Full-eye illumination ocular surface imaging of an ocular tear film for determining tear film thickness and/or providing ocular topography

ABSTRACT

Ocular surface interferometry (OSI) devices, systems, and methods are disclosed for measuring a tear film layer thickness (TFLT) of the ocular tear film, including the lipid layer thickness (LLT) and/or the aqueous layer thickness (ALT). The TFLT can be used to diagnose dry eye syndrome (DES). Certain embodiments also include ocular topography devices, systems and methods for deducing corneal shape by capturing an image of a target reflecting from the surface of the cornea. The image of the target contains topography information that is reviewable by a clinician to diagnose the health of the patient&#39;s eye by detecting corneal aberrations and/or abnormalities in corneal shape. Certain embodiments also include a combination of the OSI and ocular topography devices, systems and methods to provide imaging that can be used to yield a combined diagnosis of the patient&#39;s tear film and corneal shape.

PRIORITY APPLICATIONS

The present application is a continuation application of and claimspriority to U.S. patent application Ser. No. 14/137,105 entitled“FULL-EYE ILLUMINATION OCULAR SURFACE IMAGING OF AN OCULAR TEAR FILM FORDETERMINING TEAR FILM THICKNESS AND/OR PROVIDING OCULAR TOPOGRAPHY”filed Dec. 20, 2013, which claims priority to U.S. Provisional PatentApplication No. 61/745,213 entitled “FULL-EYE ILLUMINATION OCULARSURFACE IMAGING OF AN OCULAR TEAR FILM FOR DETERMINING TEAR FILMTHICKNESS AND/OR PROVIDING OCULAR TOPOGRAPHY” filed Dec. 21, 2012, whichare incorporated herein by reference in its entirety.

RELATED APPLICATIONS

The present application is related to U.S. patent application Ser. No.11/820,664 entitled “TEAR FILM MEASUREMENT,” filed on Jun. 20, 2007, nowissued U.S. Pat. No. 7,758,190, which is incorporated herein byreference in its entirety.

The present application is also related to U.S. patent application Ser.No. 12/633,057 entitled “TEAR FILM MEASUREMENT,” filed on Dec. 8, 2009,now issued U.S. Pat. No. 7,988,294, which is incorporated herein byreference in its entirety.

The present application is also related to U.S. patent application Ser.No. 13/195,353 entitled “TEAR FILM MEASUREMENT,” filed on Aug. 1, 2012,which is incorporated herein by reference in its entirety.

The present application is also related to U.S. patent application Ser.No. 11/900,314 entitled “TEAR FILM MEASUREMENT,” filed on Sep. 11, 2007,now issued U.S. Pat. No. 8,192,026, which is incorporated herein byreference in its entirety.

The present application is also related to U.S. patent application Ser.No. 13/455,628 entitled “TEAR FILM MEASUREMENT,” filed on Apr. 25, 2012,now issued U.S. Pat. No. 8,585,204, which is incorporated herein byreference in its entirety.

The present application is also related to U.S. patent application Ser.No. 12/798,326 entitled “OCULAR SURFACE INTERFEROMETRY (OSI) METHODS FORIMAGING AND MEASURING OCULAR TEAR FILM LAYER THICKNESS(ES),” filed onApr. 1, 2010, now issued U.S. Pat. No. 8,092,023, which is incorporatedherein by reference in its entirety.

The present application is also related to U.S. patent application Ser.No. 12/798,324 entitled “OCULAR SURFACE INTERFEROMETRY (OSI) DEVICES ANDSYSTEMS FOR IMAGING AND MEASURING OCULAR TEAR FILM LAYER THICKNESS(ES),”filed on Apr. 1, 2010, now issued U.S. Pat. No. 8,215,774, which isincorporated herein by reference in its entirety.

The present application is also related to U.S. Provisional PatentApplication Ser. No. 61/638,231 entitled “APPARATUSES AND METHODS OFOCULAR SURFACE INTERFEROMETRY (OSI) EMPLOYING POLARIZATION ANDSUBTRACTION FOR IMAGING, PROCESSING, AND/OR DISPLAYING AN OCULAR TEARFILM” filed on Apr. 25, 2012, which is incorporated herein by referencein its entirety.

The present application is also related to U.S. Provisional PatentApplication Ser. No. 61/638,260 entitled “BACKGROUND REDUCTIONAPPARATUSES AND METHODS OF OCULAR SURFACE INTERFEROMETRY (OSI) EMPLOYINGPOLARIZATION FOR IMAGING, PROCESSING, AND/OR DISPLAYING AN OCULAR TEARFILM” filed on Apr. 25, 2012, which is incorporated herein by referencein its entirety.

The present application is also related to U.S. patent application Ser.No. 12/798,325 entitled “OCULAR SURFACE INTERFEROMETRY (OSI) METHODS FORIMAGING, PROCESSING, AND/OR DISPLAYING AN OCULAR TEAR FILM,” filed onApr. 1, 2010, now issued U.S. Pat. No. 8,545,017, which claims priorityto U.S. Provisional Patent Application Ser. No. 61/211,596 entitled“OCULAR SURFACE INTERFEROMETRY (OSI) DEVICES, SYSTEMS, AND METHODS FORMEASURING TEAR FILM LAYER THICKNESS(ES),” filed on Apr. 1, 2009, whichare both incorporated herein by reference in their entireties.

The present application is also related to U.S. patent application Ser.No. 12/798,275 entitled “OCULAR SURFACE INTERFEROMETRY (OSI) DEVICES FORIMAGING, PROCESSING, AND/OR DISPLAYING AN OCULAR TEAR FILM,” filed onApr. 1, 2010, now issued U.S. Pat. No. 8,746,883, which claims priorityto U.S. Provisional Patent Application Ser. No. 61/211,596 entitled“OCULAR SURFACE INTERFEROMETRY (OSI) DEVICES, SYSTEMS, AND METHODS FORMEASURING TEAR FILM LAYER THICKNESS(ES),” filed on Apr. 1, 2009, whichare both incorporated herein by reference in their entireties.

The present application is being filed with color versions (3 sets) ofthe drawings discussed and referenced in this disclosure. Color drawingsmore fully disclose the subject matter disclosed herein. The colors astransmitted, displayed, and/or printed are subject to individual displaylimitations and cannot be expected to be an accurate representation(s);these are intended for illustrative and instructional purposes.

FIELD OF THE DISCLOSURE

The technology of the disclosure relates to imaging an ocular tear film.The technology of the disclosure also relates to measuring ocular tearfilm layer thickness(es), including lipid layer thickness (LLT) and/oraqueous layer thickness (ALT). Imaging the ocular tear film andmeasuring tear film layer thickness (TFLT) may be used to diagnose “dryeye,” which may be due to any number of deficiencies, including lipiddeficiency and aqueous deficiency.

BACKGROUND

A mammalian eye includes a cornea and sclera. The sclera provides astructure for the eye that gives the eye a generally spherical shape.The sclera also gives the major surface portion of the eye its whitecolor. The cornea is a transparent front part of the eye that covers aniris, a pupil, and an anterior chamber that is disposed in front of alens. Light passes through the transparent cornea and then through thepupil to fall upon a retina that senses the passed light. Together, theretina and a brain produce vision. Clinicians are concerned with theproper function and health of the eye.

The function of the eye can be affected by aberrations to the shape ofthe cornea. Therefore, clinical diagnosis of vision will benefit fromcapturing and displaying a corneal topography image. In essence, cornealtopography is a non-invasive procedure used to determine the shape andintegrity of the cornea of the eye. During a corneal topography, aclinician projects a series of illuminated rings known as a Placidopattern onto the surface of the cornea. The Placido pattern is reflectedback into a computerized camera system. Typically, the computerizedcamera system analyzes the reflected Placido pattern to generate atopographical map of the cornea. The resulting corneal topographicimages are analyzed by the clinician to determine the health of the eye.For example, corneal topography is used to analyze corneas before andafter vision correction surgery and for contact lens fitting, etc. It isknown that a contact lens fitting that is too tight interferes withnatural tear flow. Therefore, it is important to provide a precornealtear film analysis after a contact lens fitting.

In this regard, clinical analysis of the precorneal tear film can beprovided to improve eye health and provide comfortable vision. In thehuman eye, the precorneal tear film covering ocular surfaces is composedof three primary layers: the mucin layer, the aqueous layer, and thelipid layer. Each layer plays a role in the protection and lubricationof the eye and thus affects dryness of the eye or lack thereof. Drynessof the eye is a recognized ocular disease, which is generally referredto as “dry eye,” “dry eye syndrome” (DES), or “keratoconjunctivitissicca” (KCS). Dry eye can cause symptoms, such as itchiness, burning,and irritation, which can result in discomfort. There is a correlationbetween the ocular tear film layer thicknesses and dry eye disease. Thevarious different medical conditions and damage to the eye, as well asthe relationship of the aqueous and lipid layers to those conditions arereviewed in Sury Opthalmol 52:369-374, 2007 and additionally brieflydiscussed below.

As illustrated in FIG. 1, the precorneal tear film includes an innermostlayer of the tear film in contact with a cornea 10 of an eye 12 known asthe mucus layer 14. The mucus layer 14 is comprised of many mucins. Themucins serve to retain aqueous matter in the middle layer of the tearfilm known as the aqueous layer. Thus, the mucus layer 14 is importantin that it assists in the retention of aqueous matter on the cornea 10to provide a protective layer and lubrication, which prevents dryness ofthe eye 12.

A middle or aqueous layer 16 comprises the bulk of the tear film. Theaqueous layer 16 is formed by secretion of aqueous matter by lacrimalglands 18 and accessory tear glands 20 surrounding the eye 12, asillustrated in FIG. 2. The aqueous matter, secreted by the lacrimalglands 18 and accessory tear glands 20, is also commonly referred to as“tears.” One function of the aqueous layer 16 is to help flush out anydust, debris, or foreign objects that may get into the eye 12. Anotherimportant function of the aqueous layer 16 is to provide a protectivelayer and lubrication to the eye 12 to keep it moist and comfortable.Defects that cause a lack of sufficient aqueous matter in the aqueouslayer 16, also known as “aqueous deficiency,” are a common cause of dryeye. Contact lens wear can also contribute to dry eye. A contact lenscan disrupt the natural tear film and can reduce corneal sensitivityover time, which can cause a reduction in tear production.

The outermost layer of the tear film, known as the “lipid layer” 22 andillustrated in FIG. 1, also aids to prevent dryness of the eye. Thelipid layer 22 is comprised of many lipids known as “meibum” or “sebum”that are produced by meibomian glands 24 in upper and lower eyelids 26,28, as illustrated in FIG. 3. This outermost lipid layer is very thin,typically less than 250 nanometers (nm) in thickness. The lipid layer 22provides a protective coating over the aqueous layer 16 to limit therate at which the aqueous layer 16 evaporates. Blinking causes the uppereyelid 26 to mall up aqueous matter and lipids as a tear film, thusforming a protective coating over the eye 12. A higher rate ofevaporation of the aqueous layer 16 can cause dryness of the eye. Thus,if the lipid layer 22 is not sufficient to limit the rate of evaporationof the aqueous layer 16, dryness of the eye may result.

Notwithstanding the foregoing, it has been a long standing and vexingproblem for clinicians and scientists to quantify the lipid and aqueouslayers and any deficiencies of same to diagnose evaporative tear lossand/or tear deficiency dry eye conditions. Further, many promisingtreatments for dry eye have failed to receive approval from the UnitedStates Food and Drug Administration due to the inability to demonstrateclinical effectiveness to the satisfaction of the agency. Manyclinicians diagnose dry eye based on patient symptoms alone.Questionnaires have been used in this regard. Although it seemsreasonable to diagnose dry eye based on symptoms alone, symptoms ofocular discomfort represent only one aspect of “dry eyes,” as defined bythe National Eye Institute workshop on dry eyes. In the absence of ademonstrable diagnosis of tear deficiency or a possibility of excessivetear evaporation and damage to the exposed surface of the eye, onecannot really satisfy the requirements of dry eye diagnosis.

SUMMARY OF THE DETAILED DESCRIPTION

Full-eye illumination ocular surface imaging of ocular tear films fordetermining tear film thickness and/or providing ocular topography aredisclosed herein. Full-eye imaging means illuminating the eye and/orocular tear film with an elliptical or circular-shaped lighting patternbecause of the generally circular shape of the cornea. Full-eyeillumination does not require that the entire eye is illuminated, butrather a general elliptical or circular pattern illumination is providedto illumination a greater portion of the eye as opposed to otherpatterns of eye illumination, including square or rectangle patternillumination. Providing full-eye illumination for TFLT and/or oculartopography analysis can provide certain advantages over other patternsof eye illumination. However, there is a central region for a lensviewing opening that may be missing. This opening could optionally beoptically closed with the use of a beamsplitter to admit light fromanother location.

In this regard, certain embodiments of the detailed description includefull-eye illumination ocular surface interferometry (OSI) devices,systems, and methods for imaging an ocular tear film and/or measuring atear film layer thickness (TFLT) in a patient's ocular tear film. OSIdevices, systems, and methods can be used to provide full eyeillumination to measure the thickness of the lipid layer component (LLT)and/or the aqueous layer component (ALT) of the ocular tear film. “TFLT”as used herein includes LLT, ALT, or both LLT and ALT. “Measuring TFLT”as used herein includes measuring LLT, ALT, or both LLT and ALT. Imagingthe ocular tear film and measuring TFLT can be used in the diagnosis ofa patient's tear film, including but not limited to lipid layer andaqueous layer deficiencies. These characteristics may be the cause orcontributing factor to a patient experiencing dry eye syndrome (DES).

In other embodiments of the detailed description, full-eye illuminationocular topography devices, systems and methods for deducing cornealshape by capturing a full-eye image of a target reflecting from thesurface of the cornea are provided. The image of the target containstopography information that is reviewable by a clinician to diagnose thehealth of the patient's eye by detecting corneal aberrations and/orabnormalities in corneal shape. In cases where the ocular property iscorneal shape and a corneal topography analysis is to be conducted by aclinician, the subtraction of the at least one second image from the atleast one first image produces a Placido pattern. A typical Placidopattern comprises concentric circles and radials.

Moreover, certain other embodiments of the detailed description alsoinclude a combination of full-eye illumination OSI and ocular topographydevices, systems and methods to provide imaging that can be used toyield a combined diagnosis of the patient's tear film and corneal shape.Because embodiments provided herein include providing an OSI device formeasuring TFLT that is configured to illuminate the eye with circularshaped light patterns, the same images resulting from illumination ofthe eye in circular lighting patterns also provide circular topographyinformation about the cornea that can be observed for corneal topographyanalysis. An exemplary benefit of a combined diagnosis would be usingcorneal topography imaging for fitting contact lenses, while performinga precorneal tear film analysis and TFLT measurements before, during,and/or after the fitting of the contact lenses to ensure that thecontact lenses do not interfere with proper tear film production anddistribution.

In this regard in one tear film imaging embodiment, an imaging apparatusis provided that includes a multi-wavelength light source that isconfigured to emit light to an eye. A control system is provided in theimaging apparatus, wherein the control system is configured to spatiallymodulate light from the multi-wavelength light source to project a firstcircular pattern onto the eye, such that at least one first portion ofthe eye receives emitted light from the multi-wavelength light sourceand at least one second portion of the eye does not receive the emittedlight from the multi-wavelength light source. Providing the circular orelliptical illumination pattern provides a greater eye illumination,which is referred to herein as “full eye illumination” and “full eyeimaging.” An imaging device of the imaging apparatus receives at leastone first image containing at least one first signal associated with anocular property of the eye that comprises the emitted light reflectedfrom the at least one first portion of the eye. Light from themulti-wavelength light source is then modulated to project a secondcircular pattern onto the eye, such that the at least one first portionof the eye does not receive emitted light from the multi-wavelengthlight source and the at least one second portion on the eye receives theemitted light from the multi-wavelength light source. The imaging devicethen receives at least one second image containing at least one secondsignal associated with the ocular property of the eye comprising theemitted light reflected from the at least one second portion of the eye.The control system then subtracts the at least one second image from theat least one first image to generate at least one resulting imagecontaining a resultant signal that represents the ocular property of theeye. The image of the eye can be displayed to a technician or otheruser. The image can also be processed and analyzed to measure a TFLT inthe area or region of interest of the ocular tear film.

As provided above, the subtraction of the at least one second image fromthe at least one first image provides at least one resulting image thatis more useful in determining tear film thickness. In this regard, thefirst image is processed to subtract or substantially subtract out thebackground signal(s) superimposed upon an interference signal to reduceerror before being analyzed to measure TFLT, wherein the interferencesignal results from optical wave interference (also referred to as lightwave interference) of specularly reflected light. This is referred to as“background subtraction” in the present disclosure. The separatebackground signal(s) includes returned captured light that is notspecularly reflected from the tear film and thus does not containoptical wave interference information (also referred to as “interferenceinformation”). For example, the background signal(s) may include stray,ambient light entering into the imaging device, scattered light from thepatient's face and eye structures both outside and within the tear filmas a result of ambient light and diffuse illumination by the lightsource, and eye structure beneath the tear film, and particularlycontribution from the extended area of the source itself. The backgroundsignal(s) adds a bias (i.e., offset) error to the interference signal(s)thereby reducing interference signal strength and contrast. This errorcan adversely influence measurement of TFLT. Further, if the backgroundsignal(s) has a color hue different from the light of the light source,a color shift can also occur to the captured optical wave interference(also referred to as “interference”) of specularly reflected light, thusintroducing further error.

In one embodiment of tear film imaging, an optically “tiled” or “tiling”circular pattern illumination of the tear film is provided to provideimproved background subtraction. Tiling involves spatially controlling alight source to form specific lighting patterns on the light source whenilluminating a portion(s) in an area or region of interest on the tearfilm in a first mode to obtain specularly reflected light and backgroundsignal(s). In embodiments disclosed herein, the background signal(s) inthe second image additionally includes scattered light as a result ofdiffuse illumination by the light source providing circular patternillumination. Because background signal(s) due to scattered light as aresult of diffuse illumination by the light source is also present inthe first image, capturing a second image that includes diffuseillumination by the light source can further reduce bias (i.e., offset)error and increase interference signal strength and contrast overembodiments that do not control the light source to illuminate the tearfilm when the second image is captured.

In this regard, the light source is controlled in a first mode toprovide a circular lighting pattern to produce specularly reflectedlight from a first portion(s) in the area or region of interest of thetear film while obliquely illuminating an adjacent, second portion(s) ofthe area or region of interest of the tear film in a circular lightingpattern. The imaging device captures a first image representing theinterference of the specularly reflected light with additive backgroundsignal(s) from the first portion(s) of the area or region of interest,and background signal(s) from a second portion(s) of the area or regionof interest. The background signal(s) from the second portion(s)includes scattered light as a result of diffuse reflection of theillumination by the light source, and ambient light. The light source isthen alternately controlled in a second mode to reverse the lightingpattern of the first mode to capture specularly reflected light from thesecond portion(s) in the area or region of interest of the tear filmwhile obliquely illuminating the first portion(s) in the area or regionof interest of the tear film. The imaging device captures a second imagerepresenting the interference of the specularly reflected light and withadditive background signal(s) from the second portion(s) in the area orregion of interest on the tear film, and background signal(s) from thefirst portion(s) in the area or region of interest on the tear film. Thebackground signal(s) from the first portion(s) includes scattered lightas a result of diffuse reflection of the illumination by the lightsource. The first and second images are combined to subtract orsubstantially subtract background offset from the interference signalsto produce the resulting image. Again, the resulting image can bedisplayed on a visual display to be analyzed by a technician andprocessed and analyzed to measure a TFLT.

After the interference of the specularly reflected light is captured anda resulting image containing the interference signal is produced fromany method or device disclosed in this disclosure, the resulting imagecan also be pre-processed before being processed and analyzed to measureTFLT. Pre-processing can involve performing a variety of methods toimprove the quality of the resulting signal, including but not limitedto detecting and removing eye blinks or other signals in the capturedimages that hinder or are not related to the tear film. Afterpre-processing, the interference signal or representations thereof canbe processed to be compared against a tear film layer interference modelto measure TFLT. The interference signal can be processed and convertedby the imaging device into digital red-green-blue (RGB) component valueswhich can be compared to RGB component values in a tear filminterference model to measure TFLT on an image pixel-by-pixel basis. Thetear film interference model is based on modeling the lipid layer of thetear film in various thicknesses and mathematically or empiricallyobserving and recording resulting interference interactions ofspecularly reflected light from the tear film model when illuminated bythe light source and detected by a camera (imaging device).

Certain embodiments of the detailed description also include full-eyeocular topography devices, systems and methods for deducing cornealshape by capturing an image of a target reflecting from the surface ofthe cornea. The eye is illuminated with a circular or elliptical shapedillumination pattern, because of the cornea being circular shaped, toperform a topography of the cornea. The image of the target containstopography information that is reviewable by a clinician to diagnose thehealth of the patient's eye by detecting corneal aberrations and/orabnormalities in corneal shape. In cases where the ocular property iscorneal shape and a corneal topography analysis is to be conducted by aclinician, to improve the imaging of the eye for corneal topography, atleast one second image capture from full-eye illumination is subtractedfrom the at least one first image produces a Placido pattern. A typicalPlacido pattern comprises concentric circles and radials. Any of theaforementioned background subtraction techniques, including tiling, maybe employed.

Moreover, certain other embodiments of the detailed description alsoinclude a combination of full-eye illumination OSI and ocular topographydevices, systems and methods to provide imaging that can be used toyield a combined diagnosis of the patient's tear film and corneal shape.Because embodiments provided herein include providing an OSI device formeasuring TFLT that is configured to illuminate the eye with circularshaped light patterns, the same images resulting from illumination ofthe eye in circular lighting patterns also provide circular topographyinformation about the cornea that can be observed for corneal topographyanalysis. An exemplary benefit of a combined diagnosis would be usingcorneal topography imaging for fitting contact lenses, while performinga precorneal tear film analysis and TFLT measurements before, during,and/or after the fitting of the contact lenses to ensure that thecontact lenses do not interfere with proper tear film production anddistribution.

In this regard, certain embodiments disclosed herein include a lightmodulator system that is communicatively coupled to the control systemto spatially modulate light from the multi-wavelength light source toalternately project the first circular pattern and the second circularpattern onto the eye to illuminate the ocular property therebygenerating the first signal and the second signal of the ocularproperty. Moreover, in one embodiment, the light modulator systemincludes a disk disposed between the imaging device and eye forsequentially projecting the first circular pattern and the secondcircular pattern onto the eye when the disk is illuminated, and whereinthe disk includes a central aperture for the imaging device to receivelight reflected from the eye. In one embodiment, the disk is rotatableand is patterned with a plurality of concentric circles havingalternating opaque and translucent sections with edges that formradials. The disk is rotated under the control of the control system togenerate the first circular pattern and the second circular pattern. Inyet another embodiment, the disk is made up of a substrate having pixelsthat are controllable by a controller. Instead of rotating the disk togenerate the first and second circular patterns, the pixels arecontrollable to transition between dark and light in response to signalstransmitted from the controller. It is to be understood that thecontrollable pixels can do more than invert the light and dark regions.A pattern of pixels can scan and/or use various pattern types to providemany more points for higher resolutions and more quantifiabletopography. Ultimately, either embodiment produces images that areusable for determining ocular properties of the eye. As discussed above,one such ocular property is ocular tear film thickness.

Beyond ocular tear film measurement, embodiments of the presentdisclosure are also configured to generate a Placido pattern fordetermining another ocular property, which may be corneal shape. In thisregard, embodiments disclosed herein yield a benefit of being usable foranalyzing an ocular topography. For example, subtracting the at leastone second image from the at least one first image generates at leastone resulting image that is a Placido pattern that comprises concentriccircles and radials. Irregularities such as warped radials and skewedcircles captured in the Placido pattern of a resulting image(s) indicateabnormalities of the corneal surface. In order to assist a diagnosis ofsuch abnormalities, the Placido pattern within the resulting image isviewable on a visual display. Better yet, embodiments of the presentdisclosure are usable to correlate aberrations of the corneal tear filmwith abnormalities of the corneal surface.

In this regard, the first ocular property may be a thickness of anocular tear film and the second ocular property may be corneal shape. Inoperation, the embodiments of the present disclosure illuminate theocular tear film and project a first circular pattern onto the tear filmto produce specularly reflected light from the first portion(s) of theocular tear film while non-specular illuminating second adjacentportions of the ocular tear film. A first image(s) of the eye thatincludes the first circular pattern and specular reflections from thetear film is captured by the imaging device. Next, the control systeminverts the first circular pattern to provide a second circular pattern.A second image(s) of the eye that includes the second circular patternwith specular reflections from the tear film is captured by the imagingdevice. The first and second images are combined to provide a thirdcircular pattern containing tear film thickness information and cornealtopography information. It is to be understood that the first and secondimages can be combined to generate various other patterns useful for eyehealth assessment and analysis. In at least one embodiment, the thirdcircular pattern is a Placido pattern having concentric rings andradials. In this case, the Placido pattern includes tear film thicknessinformation between the concentric circles and radials, while theconcentric circles and radials of the Placido disk contain the cornealtopography information. A benefit of this embodiment providing combinedfunctions of tear film thickness measurement and ocular topographydisplay by using of the circular patterns to capture reflected lightfrom the eye in concentric circles and/or radials. As such, the presentembodiments provide substantial purchase cost and operational costsavings over tradition ocular instruments by integrating tear filmthickness measurement and ocular topography display functions into oneOSI device. It is to be understood that while circular patterns may bepreferable, a rectangular grid or rectangular checkerboard pattern isalso usable for full eye analysis of tear film and topography. Arectangular pattern might need to be somewhat larger than a circularpattern; however, with computerized analysis profilometry can still beperformed.

Those skilled in the art will appreciate the scope of the presentdisclosure and realize additional aspects thereof after reading thefollowing detailed description of the preferred embodiments inassociation with the accompanying drawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

The accompanying drawing figures incorporated in and forming a part ofthis specification illustrate several aspects of the disclosure, andtogether with the description serve to explain the principles of thedisclosure. Note that drawing figures that include photographs of realeyes also include prophetic image overlays of patterns of diffuse andspecularly reflected light. In particular, FIGS. 7A, 7B, 7C, 20, 21A,21B, 22, 23, 27A, 27B, 27C, 35, 42, 43, 44, and 45 include propheticimage overlays.

FIG. 1 is a side view of an exemplary eye showing the three layers ofthe tear film in exaggerated form;

FIG. 2 is a front view of an exemplary eye showing the lacrimal andaccessory tear glands that produce aqueous in the eye;

FIG. 3 illustrates exemplary upper and lower eyelids showing themeibomian glands contained therein;

FIGS. 4A and 4B are illustrations of an exemplary light source andimaging device to facilitate discussion of illumination of the tear filmand capture of interference interactions of specularly reflected lightfrom the tear film and for providing ocular topography images;

FIG. 5 illustrates (in a microscopic section view) exemplary tear filmlayers to illustrate how light rays can specularly reflect from varioustear film layer transitions to produce light wave interference;

FIG. 6 is a flowchart of an exemplary process for obtaining one or moreinterference signals from images of a tear film representing specularlyreflected light from the tear film with background signal subtracted orsubstantially subtracted;

FIG. 7A illustrates a first image focused on a lipid layer of a tearfilm and capturing interference interactions of specularly reflectedlight from an area or region of interest of the tear film;

FIG. 7B illustrates a second image focused on the lipid layer of thetear film in FIG. 7A and capturing background signal when notilluminated by the light source;

FIG. 7C illustrates an image of the tear film when background signalcaptured in the second image of FIG. 7B is subtracted from the firstimage of FIG. 7A;

FIG. 8A is an exemplary first circular pattern having concentric circleswith alternating opaque tiles and translucent tiles that have edges thatform radials;

FIG. 8B is an exemplary second circular pattern that is the inversecontrast of the first circular pattern;

FIG. 9 is a perspective view of an exemplary ocular surfaceinterferometry (OSI) device for illuminating and imaging a patient'stear film, displaying images, analyzing the patient's tear film,generating results from the analysis of the patient's tear film and forproviding ocular topography images;

FIG. 10 is a side view of the OSI device of FIG. 9 illuminating andimaging a patient's eye and tear film;

FIG. 11 is a side view of a video camera and illuminator within the OSIdevice of FIG. 9 imaging a patient's eye and tear film;

FIG. 12 is a flowchart of an exemplary process for corneal topographymapping using the OSI device of FIGS. 4A and 4B or the OSI device ofFIGS. 9-11.

FIG. 13 is an exemplary corneal topography mapping Placido patternresulting from the exemplary process for corneal topography mappingdepicted in the flowchart of FIG. 12;

FIG. 14 is a rearview of a prior art checkered Placido apparatus;

FIG. 15 is a side view of the prior art checkered Placido imageprojected onto a cornea;

FIG. 16 is a flowchart of an exemplary process of measuring tear filmthickness combined with corneal topography mapping using the OSI deviceof FIGS. 4A and 4B or the OSI device of FIGS. 9-11;

FIG. 17A illustrates an exemplary system diagram of a control system andsupporting components in the OSI device of FIGS. 9-11;

FIG. 17B is a flowchart illustrating an exemplary overall processingflow of the OSI device of FIGS. 9-11 having systems components accordingto the exemplary system diagram of the OSI device in FIG. 17A;

FIG. 18 is a flowchart illustrating exemplary pre-processing stepsperformed on the combined first and second images of a patient's tearfilm before measuring tear film layer thickness (TFLT);

FIG. 19 is an exemplary graphical user interface (GUI) for controllingimaging, pre-processing, and post-processing settings of the OSI deviceof FIGS. 9-11;

FIG. 20 illustrates an example of a processed image in an area or regionof interest of a tear film containing specularly reflected light fromthe tear film overlaid on top of a background image of the tear film;

FIGS. 21A and 21B illustrate exemplary threshold masks that may be usedto provide a threshold function during pre-processing of a resultingimage containing specularly reflected light from a patient's tear film;

FIG. 22 illustrates an exemplary image of FIG. 20 after a thresholdpre-processing function has been performed leaving interference of thespecularly reflected light from the patient's tear film;

FIG. 23 illustrates an exemplary image of the FIG. 22 image after erodeand dilate pre-processing functions have been performed on the image;

FIG. 24 illustrates an exemplary histogram used to detect eye blinksand/or eye movements in captured images or frames of a tear film;

FIG. 25 illustrates an exemplary process for loading an InternationalColour Consortium (ICC) profile and tear film interference model intothe OSI device of FIG. 9-11;

FIG. 26 illustrates a flowchart providing an exemplary visualizationsystem process for displaying images of a patient's tear film on adisplay in the OSI device of FIG. 9-11;

FIGS. 27A-27C illustrate exemplary images of a patient's tear film witha tiled pattern of interference interactions from specularly reflectedlight from the tear film displayed on a display;

FIG. 28 illustrates an exemplary post-processing system that may beprovided in the OSI device of FIG. 9;

FIG. 29A illustrates an exemplary 3-wave tear film interference modelbased on a 3-wave theoretical tear film model to correlate differentobserved interference colors with different lipid layer thicknesses(LLTs) and aqueous layer thicknesses (ALTs);

FIG. 29B illustrates another exemplary 3-wave tear film interferencemodel based on a 3-wave theoretical tear film model to correlatedifferent observed interference colors with different lipid layerthicknesses (LLTs) and aqueous layer thicknesses (ALTs);

FIG. 30 is another representation of the 3-wave tear film interferencemodel of FIGS. 29A and 29B with normalization applied to eachred-green-blue (RGB) color value individually;

FIG. 31 is an exemplary histogram illustrating results of a comparisonof interference interactions from the processed interference signal ofspecularly reflected light from a patient's tear film to the 3-wave tearfilm interference model of FIGS. 29A, 29B, and 30 for measuring TFLT ofa patient's tear film;

FIG. 32 is an exemplary histogram plot of distances in pixels betweenRGB color value representation of interference interactions from theprocessed interference signal of specularly reflected light from apatient's tear film and the nearest distance RGB color value in the3-wave tear film interference model of FIGS. 29A, 29B, and 30;

FIG. 33 is an exemplary threshold mask used during pre-processing of thetear film images;

FIG. 34 is an exemplary three-dimensional (3D) surface plot of themeasured LLT and ALT thicknesses of a patient's tear film;

FIG. 35 is an exemplary image representing interference interactions ofspecularly reflected light from a patient's tear film results windowbased on replacing a pixel in the tear film image with the closestmatching RGB color value in the normalized 3-wave tear film interferencemodel of FIG. 30;

FIG. 36 is an exemplary TFLT palette curve for a TFLT palette of LLTsplotted in RGB space for a given ALT in three-dimensional (3D) space;

FIG. 37 is an exemplary TFLT palette curve for the TFLT palette of FIG.36 with LLTs limited to a maximum LLT of 240 nm plotted in RGB space fora given ALT in three-dimensional (3D) space;

FIG. 38 illustrates the TFLT palette curve of FIG. 37 with an acceptabledistance to palette (ADP) filter shown to discriminate tear film pixelvalues having RGB values that correspond to ambiguous LLTs;

FIG. 39 is an exemplary login screen to a user interface system forcontrolling and accessing the OSI device of FIG. 9-11;

FIG. 40 illustrates an exemplary interface screen for accessing apatient database interface in the OSI device of FIG. 9-11;

FIG. 41 illustrates a patient action control box for selecting to eithercapture new tear film images of a patient in the patient database orview past captured images of the patient from the OSI device of FIGS.9-11;

FIG. 42 illustrates a viewing interface for viewing a patient's tearfilm either captured in real-time or previously captured by the OSIdevice of FIGS. 9-11;

FIG. 43 illustrates a tear film image database for a patient;

FIG. 44 illustrates a view images GUI screen showing an overlaid imageof interference interactions of the interference signals from specularlyreflected light from a patient's tear film overtop an image of thepatient's eye for both the patient's left and right eyes side by side;and

FIG. 45 illustrates the GUI screen of FIG. 44 with the images of thepatient's eye toggled to show only the interference interactions of theinterference signals from specularly reflected light from a patient'stear film.

DETAILED DESCRIPTION

The embodiments set forth below represent the necessary information toenable those skilled in the art to practice the disclosure andillustrate the best mode of practicing the disclosure. Upon reading thefollowing description in light of the accompanying drawing figures,those skilled in the art will understand the concepts of the disclosureand will recognize applications of these concepts not particularlyaddressed herein. It should be understood that these concepts andapplications fall within the scope of the disclosure and theaccompanying claims.

Ocular surface imaging of ocular tear films and ocular topography areprovided herein. Embodiments of the detailed description include ocularsurface interferometry (OSI) devices, systems, and methods for imagingan ocular tear film and/or measuring a tear film layer thickness (TFLT)in a patient's ocular tear film. The OSI devices, systems, and methodscan be used to measure the thickness of the lipid layer thickness (LLT)component and/or the aqueous layer thickness (ALT) component of theocular tear film. “TFLT” as used herein includes LLT, ALT, or both LLTand ALT. “Measuring TFLT” as used herein includes measuring LLT, ALT, orboth LLT and ALT. Imaging the ocular tear film and measuring TFLT can beused in the diagnosis of a patient's tear film, including but notlimited to lipid layer and aqueous layer deficiencies. Thesecharacteristics may be the cause or contributing factor to a patientexperiencing dry eye syndrome (DES).

In this regard, embodiments disclosed herein provide a full eye imagingapparatus for determining ocular properties of the eye, including TFLTand ocular surface properties. Full-eye imaging means illuminating theeye with a circular lighting pattern to be compatible with the circularshape of the cornea. A further advantage of the disclosed simultaneousdual properties measurement (TFLT and topography) is that cornealtopographical measurements can be corrected for variations in tear filmthickness, and in particular ALT.

Certain embodiments of the detailed description also include oculartopography devices, systems and methods for deducing corneal shape bycapturing an image of a target reflecting from the surface of thecornea. The image of the target contains topography information that isreviewable by a clinician to diagnose the health of the patient's eye bydetecting corneal aberrations and/or abnormalities in corneal shape. Incases where the ocular property is corneal shape and a cornealtopography analysis is to be conducted by a clinician, the subtractionof the at least one second image from the at least one first imageproduces a Placido pattern. A typical Placido pattern comprisesconcentric circles and radials.

Moreover, certain other embodiments of the detailed description alsoinclude a combination of OSI and ocular topography devices, systems andmethods to provide imaging that can be used to yield a combineddiagnosis of the patient's tear film and corneal shape. Becauseembodiments provided herein include providing an OSI device formeasuring TFLT that is configured to illuminate the eye with circularshaped light patterns, the same images resulting from illumination ofthe eye in circular lighting patterns also provide circular topographyinformation about the cornea that can be observed for corneal topographyanalysis. An exemplary benefit of a combined diagnosis would be usingcorneal topography imaging for fitting contact lenses, while performinga precorneal tear film analysis and TFLT measurements before, during,and/or after the fitting of the contact lenses to ensure that thecontact lenses do not interfere with proper tear film production anddistribution.

Exemplary OSI Device with Motorised Placido Disk

In this regard, FIGS. 4A-4B illustrate a general embodiment of an ocularsurface interferometry (OSI) device 30 for providing ocular surfaceimaging of ocular tear film and ocular topography. Other embodimentswill be described later in this application. In general, the OSI device30 is configured to illuminate a patient's ocular tear film, captureimages of interference interactions of specularly reflected light fromthe ocular tear film, and process and analyze the interferenceinteractions to measure TFLT. As shown in FIG. 4A, the exemplary OSIdevice 30 positioned in front of one of the patient's eye 32 is shownfrom a side view. A top view of the patient 34 in front of the OSIdevice 30 is illustrated in FIG. 4B. The ocular tear film of a patient'seyes 32 is illuminated with a light source 36 (also referred to hereinas “illuminator 36”) and comprises a large area light source having aspectrum in the visible region adequate for TLFT measurement andcorrelation to dry eye. The illuminator 36 can be a white ormulti-wavelength light source and in this exemplary embodiment is madeup of an array of light emitting diodes (LEDs) 38. An optional diffusercan be included to improve the uniformity of the LEDs 38.

In this embodiment, the illuminator 36 is a Lambertian emitter and isadapted to be positioned in front of the patient's eye 32. As employedherein, the terms “Lambertian surface” and “Lambertian emitter” aredefined to be a light emitter having equal or substantially equal (alsoreferred to as “uniform” or substantially uniform) intensity in allpertinent directions. This allows the imaging of the reflection of auniformly or substantially uniformly bright tear film region for TFLT,as discussed in more detail in this disclosure. The illuminator 36comprises a large surface area emitter, arranged such that rays emittedfrom the emitter are specularly reflected from the ocular tear film andundergo constructive and destructive interference in tear film layerstherein. An image of the patient's 34 lipid layer is the backdrop overwhich the interference image is seen and it should be as spatiallyuniform as possible. Although it is convenient to have the illuminator36 emit light in a substantially spatially uniform manner, it should beunderstood that a calibration and correction for less spatially uniformlight emissions can be accomplished via processing using a processor ofthe OSI device 30.

A Placido disk 40 is disposed between the illuminator 36 and the patient34. A cut-away along a line A-A′ depicts the Placido disk 40 in thisexemplary embodiment as having a circular pattern 42 includingconcentric circles 44 with alternating opaque tiles 46 and translucenttiles 48 that have edges that form radials 50. The exemplary OSI device30 includes an electric motor 52 coupled to a drive mechanism 54 forrotating the Placido disk 40 around an optical axis 41. In thisparticular embodiment, the Placido disk 40 is rotatably coupled to theilluminator 36 which in turn is attached to an imaging device 56included in the OSI device 30. The Placido disk 40 may be a flexible,acrylic plastic sheet that is patterned with a circular pattern havingconcentric circles, radials, and alternating opaque tiles andtranslucent tiles. The Placido disk 40 also includes a centrally locatedaperture 60 through which the imaging device 56 receives light.

In operation, a controller 58 synchronizes the rotation of the Placidodisk 40 with the capturing of images via the imaging device 56. Inparticular, the imaging device 56 is employed to capture interferenceinteractions of specularly reflected light from the patient's 34 oculartear film when illuminated by the illuminator 36. A desired portion ofthe specularly reflected light passes through the aperature 60 in thePlacido disk 40 to impinge upon an imaging lens 62 of the imaging device56. A stand 64 carries the imaging device 56 and the electric motor 52.The stand 64 allows for height adjustment of the imaging device 56 alonga Y-AXIS. The stand 64 is also movable along an X-AXIS for positioningthe imaging device 56 relative to the patient 34. The imaging device 56may be a still or video camera, or other device that captures images andproduces an output signal representing information in captured images.The output signal may be a digital representation of the capturedimages.

The geometry of the illuminator 36 can be understood by starting fromthe imaging lens 62 of the imaging device 56 and proceeding forward tothe patient's eye 32 and then to the illuminator 36. The fundamentalequation for tracing ray lines is Snell's law, which provides:n1 Sin Θ₁ =n2 Sin Θ₂,where “n1” and “n2” are the indexes of refraction of two mediumscontaining the ray, and Θ₁ and Θ₂ are the angles of the ray relative tothe normal from the transition surface. As illustrated in FIG. 5, lightrays 66 are directed by the illuminator 36 to an ocular tear film 68. Inthe case of specularly reflected light 70 that does not enter a lipidlayer 72 and instead reflects from an anterior surface 74 of the lipidlayer 72, Snell's law reduces down to Θ₁=Θ₂, since the index ofrefraction does not change (i.e., air in both instances). Under theseconditions, Snell's law reduces to the classical law of reflection suchthat the angle of incidence is equal and opposite to the angle ofreflectance.

Some of the light rays 76 pass through the anterior surface 74 of thelipid layer 72 and enter into the lipid layer 72, as illustrated in FIG.5. As a result, the angle of these light rays 76 (i.e., Θ₃) normal tothe anterior surface 74 of the lipid layer 72 will be different than theangle of the light rays 66 (Θ₁) according to Snell's law. This isbecause the index of refraction of the lipid layer 72 is different thanthe index of refraction of air. Some of the light rays 76 passingthrough the lipid layer 72 will specularly reflect from the lipidlayer-to-aqueous layer transition 78 thereby producing specularlyreflected light rays 80. The specularly reflected light rays 70, 80undergo constructive and destructive interference anterior of the lipidlayer 72. The modulations of the interference of the specularlyreflected light rays 70, 80 superimposed on the anterior surface 74 ofthe lipid layer 72 are collected by the imaging device 56 (FIGS. 4A and4B) when focused on the anterior surface 74 of the lipid layer 72.Focusing the imaging device 56 on the anterior surface 74 of the lipidlayer 72 allows capturing of the modulated interference information atthe plane of the anterior surface 74. In this manner, the capturedinterference information and the resulting calculated TFLT from theinterference information is spatially registered to a particular area ofthe tear film 68 since the calculated TFLT can be associated with suchparticular area, if desired.

The thickness of the lipid layer 72 (‘d₁’) is a function of theinterference interactions between specularly reflected light rays 70,80. The thickness of the lipid layer 72 (‘d₁’) is on the scale of thetemporal (or longitudinal) coherence of the illuminator 36. Therefore,thin lipid layer films on the scale of one wavelength of visible lightemitted by the illuminator 36 offer detectable colors from theinterference of specularly reflected light when viewed by a camera orhuman eye. The colors may be detectable as a result of calculationsperformed on the interference signal and represented as digital valuesincluding, but not limited to, a red-green-blue (RGB) value in the RGBcolor space. Quantification of the interference of the specularlyreflected light can be used to measure LLT. The thicknesses of anaqueous layer 82 (‘d₂’) can also be determined using the same principle.Some of the light rays 76 (not shown) passing through the lipid layer 72can also pass through the lipid layer-to-aqueous layer transition 78 andenter into the aqueous layer 82 specularly reflecting from theaqueous-to-mucin/cornea layer transition 84. These specular reflectionsalso undergo interference with the specularly reflected light rays 70,80. The magnitude of the reflections from each interface depends on therefractive indices of the materials as well as the angle of incidence,according to Fresnel's equations, and so the depth of the modulation ofthe interference interactions is dependent on these parameters, thus sois the resulting color.

Turning back to FIGS. 4A and 4B, the illuminator 36 in this embodimentis a broad spectrum light source covering the visible region betweenabout 400 nm to about 700 nm. The illuminator 36 contains an arced orcurved housing 88 (see FIG. 4B) into which the LEDS 38 are mounted,subtending an arc of approximately 130 degrees from the optical axis 41of the patient's eye 32 (see FIG. 4B). A curved surface may presentbetter uniformity and be more efficient, as the geometry yields asmaller device to generating a given intensity of light. The total powerradiated from the illuminator 36 should be kept to a minimum to preventaccelerated tear evaporation. Light entering the pupil can cause reflextearing, squinting, and other visual discomforts, all of which affectTFLT measurement accuracy.

In order to prevent alteration of the proprioceptive senses and reduceheating of the tear film 68, incident power and intensity on thepatient's eye 32 may be minimized and thus, the step of collecting andfocusing the specularly reflected light may be carried out by theimaging device 56. The imaging device 56 may be a video camera, slitlamp microscope, or other observation apparatus mounted on the stand 64,as illustrated in FIGS. 4A and 4B. Detailed visualization of the imagepatterns of the tear film 68 involves collecting the specularlyreflected light 90 (see FIG. 4B) and focusing the specularly reflectedlight 90 at the lipid layer 72 such that the interference interactionsof the specularly reflected light from the ocular tear film areobservable.

In the embodiment shown in FIGS. 4A-4B, a second image is captured whenthe tear film is obliquely illuminated by the illuminator 36 usingillumination that possesses the same or nearly the same average geometryand illuminance level as used to produce specularly reflected light froma tear film. In this manner, the background signal captured in thesecond image contains the equivalent background signal present in thefirst image including scattered light from the tear film and patient'seye as a result of diffuse illumination by the illuminator 36. Thesecond image also includes a representative signal of eye structurebeneath the tear film because of the equivalent lighting when theilluminator 36 is activated when capturing the second image. In theembodiment of FIGS. 4A and 4B, the Placido disk 40 provides a “tiled” or“tiling” illumination of the tear film. Tiling allows a light source toilluminate a sub-area(s) of interest on the tear film to obtainspecularly reflected light while at the same time non-specularlyilluminating adjacent sub-area(s) of interest of the tear film to obtainscattered light as a result of diffuse illumination by the illuminator36. In this manner, the subtracted background signal includes scatteredlight as a result of diffuse illumination by the illuminator 36 to allowfurther reduction of offset bias (i.e., offset) error and to therebyincrease interference signal purity and contrast.

In this regard, as illustrated in FIG. 6, the process starts byadjusting the patient 34 with regard to the illuminator 36 and theimaging device 56 (block 92). The illuminator 36 is controlled toilluminate the patient's 34 tear film. The imaging device 56 is locatedappropriately and is controlled to be focused on the lipid layer suchthat the interference interactions of specularly reflected light fromthe tear film are observable when the tear film is illuminated.Thereafter, light emitted from the illuminator 36 is modulated via thePlacido disk 40 in a first “tiling” mode in which a first circularpattern 42A (FIG. 8A) is projected onto the patient's 34 tear film toproduce specularly reflected light from a first area(s) of interest ofthe tear film while non-specularly illuminating an adjacent, secondarea(s) of interest of the tear film (block 94). Specifically, thecircular pattern 42 of the Placido disk 40 is projected onto thepatient's eye 32.

An example of a first image 120 captured of a patient's eye 121 and tearfilm 123 by the imaging device 56 when the illuminator 36 produces thecircular pattern 42 in the first mode is illustrated by example in FIG.7A. In this example, the illuminator 36 and Placido disk 40 arecontrolled to provide a first tiled illumination pattern on the tearfilm 123. While illumination of the tear film 123 is in the first mode,the imaging device 56 captures the first image 120 of the patient's eye121 and the tear film 123 (block 96). As illustrated in FIG. 7A, thefirst image 120 of the patient's eye 121 has been illuminated so thatspecularly reflected light is produced in first portions 126A of thetear film 123. The interference signal(s) from the first portions 126Ainclude interference from specularly reflected light along with additivebackground signal, which includes scattered light signal as a result ofdiffuse illumination from the illuminator 36. Again, the illuminator 36and the imaging device 56 may be controlled to illuminate the tear film123 that does not include the pupil of the eye 121 so as to reducereflex tearing. The illuminator 36 may be flashed in block 94 to producespecularly reflected light from the first portions 126A, whereby theimaging device 56 is synchronized with the frequency of the projectionof the circular pattern 42 in block 96 to capture the first image 120 ofthe patient's eye 121 and the tear film 123.

Also during the first mode, the illuminator 36 obliquely illuminatesadjacent second portions 128A to the first portions 126A on the eye 121,as shown in the first image 120 in FIG. 7A. The second portions 128Ainclude comparable background offset present in the first portion(s)126A, which includes scattered light signal as a result of diffuseillumination from the illuminator 36 since the illuminator 36 is turnedon when the first image 120 is captured by the imaging device 56.Further, the eye 121 structures beneath the tear film 123 are capturedin the second portions 128A due to the diffuse illumination by theilluminator 36. Moreover, in this embodiment, the area of the tear film123 is broken into two portions at the same time: first portions 126Aproducing specularly reflected light combined with background signal,and second portions 128A diffusedly illuminated by the illuminator 36and containing background signal, which includes scattered light fromthe illuminator 36. The imaging device 56 produces a first output signalthat contains a representation of the first portions 126A and the secondportions 128A.

Next, the illuminator 36 and the Placido disk 40 are controlled in asecond mode to invert the first circular pattern 42A (FIG. 8A) from thefirst mode when illuminating the tear film 123 (block 98, FIG. 6). Anexemplary method usable to invert the first circular pattern can bebetter understood by turning to FIGS. 8A and 8B. In FIG. 8A, the firstcircular pattern 42A is in a first mode in which an outer one of thetranslucent tiles 48 is located between 0 radians and π/4 radians. Thesecond mode shown in FIG. 8B occurs after the first circular pattern 42Ais rotated by π/4 radians in either direction. In the second mode, anouter one of the opaque tiles 46 is now located between 0 radians andπ/4 radians. As such, all of the opaque tiles 46 and all of thetranslucent tiles 48 have been effectively inverted (i.e. swapped)between the first mode and the second mode. It is to be understood thatan angle of rotation (N) necessary for Placido disk 40 to invert theopaque tiles 46 and the translucent tiles 48 is a function of the numberof radials (R) that separate the opaque tiles 46 and the translucenttiles 48. The angle of rotation N is equal to 2π/R.

Returning to FIG. 6, a second image 130 of the tear film 123 in thesecond mode, as illustrated by example in FIG. 7B (block 100, FIG. 6).As shown in the second image 130 in FIG. 7B, the second portions 128A inthe first image 120 of FIG. 7A are now second portions 128B in thesecond image 130 in FIG. 7B containing specularly reflected light fromthe tear film 123 with additive background signal. The first portions126A in the first image 120 of FIG. 7A are now first portions 126B inthe second image 130 in FIG. 7B containing background signal withoutspecularly reflected light. Again, the background signal in the firstportions 126B includes scattered light signal as a result of diffuseillumination by the illuminator 36. The imaging device 56 produces asecond output signal of the second image 130 in FIG. 7B. The illuminator36 may also be flashed in block 98 to produce specularly reflected lightfrom the second portions 128B, whereby the imaging device 56 issynchronized with the frequency of the projection of the second circularpattern in block 98 to capture the second image 130 of the patient's eye32 and the tear film 123.

The first and second output signals can then be combined to produce aresulting signal comprised of the interference signal of the specularlyreflected light from the tear film 123 with background signal subtractedor substantially removed from the interference signal (block 102, FIG.6). A resulting image is produced as a result of having interferenceinformation from the specularly reflected light from the tear film 123with background signal eliminated or reduced, including backgroundsignal resulting from scattered light from diffuse illumination by theilluminator 36 (block 104, FIG. 6). An example of a resulting image 132in this regard is illustrated in FIG. 7C. The resulting image 132represents the first output signal represented by the first image 120 inFIG. 7A combined with the second output signal represented by the secondimage 130 in FIG. 7B. As illustrated in FIG. 7C, interference signals ofspecularly reflected light from the tear film 123 are provided for boththe first and second portions 126, 128 of the tear film 123. Thebackground signal has been eliminated or reduced. As can be seen in FIG.7C, the signal purity and contrast of the interference signalrepresenting the specularly reflected light from the tear film 123 fromfirst and second portions 126, 128 appears more vivid and higher incontrast than the interference interaction would without spatiallymodulating the light emitted from the illuminator 36 by using thePlacido disk 40 to project the circular patterns 42A and 42B (FIGS. 8Aand 8B).

In the discussion of the example first and second images 120, 130 inFIGS. 7A and 7B above, each first portion 126 can be thought of as afirst image, and each second portion 128 can be thought of as a secondimage. Thus, when the first and second portions 126A, 128B are combinedwith corresponding first and second portions 126B, 128A, this is akin tosubtracting second portions 126B, 128A from the first portions 126A,128B, respectively.

In the example of FIGS. 6-7C, the first image and second image 120, 130contain a plurality of portions or tiles. The number of tiles depends onthe resolution of lighting interactions provided for and selected forthe illuminator 36 to produce the first and second modes of illuminationto the tear film 123. The illumination modes can go from one extreme ofone tile to any number of tiles desired. Each tile can be the size ofone pixel in the imaging device 56 or areas covering more than one pixeldepending on the capability of the illuminator 36 and the imaging device56. The number of tiles can affect accuracy of the interference signalsrepresenting the specularly reflected light from the tear film.Providing too few tiles in a tile pattern can limit the representativeaccuracy of the average illumination geometry that produces thescattered light signal captured by the imaging device 56 in the portions128A and 126B for precise subtraction from portions 128B and 126Arespectively.

Note that while this example in FIGS. 6-7C discusses a first image and asecond image captured by the imaging device 56 and a resulting firstoutput signal and second output signal, the first image and the secondimage may comprise a plurality of images taken in a time-sequencedfashion. If the imaging device 56 is a video camera, the first andsecond images may contain a number of sequentially-timed frames governedby the frame rate of the imaging device 56. The imaging device 56produces a series of first output signals and second output signals. Ifmore than one image is captured, the subtraction performed in a firstimage should ideally be from a second image taken immediately after thefirst image so that the same or substantially the same lightingconditions exist between the images so the background signal in thesecond image is present in the first image, and more importantly, sothat movement of the eye and especially of the tear-film dynamic isminimal between subtracted frames. The subtraction of the second outputsignal from the first output signal can be performed in real time.Alternatively, the first and second output signals can be recorded andprocessed at a later time.

Exemplary OSI Device with an Electronic Placido Disk

The above discussed illustrations provide examples of illuminating andimaging a patient's TFLT. These principles are described in more detailwith respect to a specific example of an OSI device 170 illustrated inFIGS. 14-48 and described below throughout the remainder of thisapplication. The OSI device 170 can illuminate a patient's tear film,capture interference information from the patient's tear film, andprocess and analyze the interference information to measure TFLT.Further, the OSI device 170 includes a number of optional pre-processingfeatures that may be employed to process the interference signal in theresulting signal to enhance TFLT measurement. The OSI device 170 mayinclude a display and user interface to allow a physician or technicianto control the OSI device 170 to image a patient's eye and tear film andmeasure the patient's TFLT.

Illumination and Imaging

In this regard, FIG. 9 illustrates a perspective view of the OSI device170. The OSI device 170 is designed to facilitate imaging of thepatient's ocular tear film and processing and analyzing the images todetermine characteristics regarding a patient's tear film. The OSIdevice 170 includes an imaging device and light source in this regard,as will be described in more detail below. As illustrated in FIG. 9, theOSI device 170 is comprised generally of a housing 172, a displaymonitor (“display”) 174, and a patient head support 176. The housing 172may be designed for table top placement. The housing 172 rests on a base178 in a fixed relationship. As will be discussed in more detail below,the housing 172 houses an imaging device and other electronics,hardware, and software to allow a clinician to image a patient's oculartear film. A light source 173 (also referred to herein as “illuminator173”) is also provided inside the housing 172 and is provided behind aPlacido disk 175. Unlike the Placido disk 40 of the OSI device 30 (FIGS.4A and 4B), the Placido disk 175 of the OSI device 170 of thisembodiment is not physically rotatable. Instead, the Placido disk 175 isan electronic screen made up of a substrate having pixels that arecontrollable by a controller. The pixels are controllable to transitionbetween dark and light in response to signals transmitted from thecontroller. Similar to the Placido disk 40 of the OSI device 30 (FIGS.4A and 4B), the Placido disk 175 includes a centrally located aperture177 through which the imaging device receives light reflected from thepatient's 184 eye 192 (Shown in FIG. 10).

To image a patient's ocular tear film, the patient places his or herhead in the patient head support 176 and rests his or her chin on a chinrest 180. The chin rest 180 can be adjusted to align the patient's eyeand tear film with the imaging device inside the housing 172, as will bediscussed in more detail below. The chin rest 180 may be designed tosupport up to two (2) pounds of weight, but such is not a limitingfactor. A transparent window 177 allows the imaging device inside thehousing 172 to have a clear line of sight to a patient's eye and tearfilm when the patient's head is placed in the patient head support 176.The OSI device 170 is designed to image one eye at a time, but can beconfigured to image both eyes of a patient, if desired.

In general, the display 174 provides input and output from the OSIdevice 170. For example, a user interface can be provided on the display174 for the clinician to operate the OSI device 170 and to interact witha control system provided in the housing 172 that controls the operationof the OSI device 170, including an imaging device, an imaging devicepositioning system, a light source, other supporting hardware andsoftware, and other components. For example, the user interface canallow control of imaging positioning, focus of the imaging device, andother settings of the imaging device for capturing images of a patient'socular tear film. The control system may include a general purposemicroprocessor or computer with memory for storage of data, includingimages of the patient's eye and tear film. The microprocessor should beselected to provide sufficient processing speed to process images of thepatient's tear film and generate output characteristic information aboutthe tear film (e.g., one minute per twenty second image acquisition).The control system may control synchronization of activation of thelight source and the imaging device to capture images of areas ofinterest on the patient's ocular tear film when properly illuminated.Various input and output ports and other devices can be provided,including but not limited to a joystick for control of the imagingdevice, USB ports, wired and wireless communication including Ethernetcommunication, a keyboard, a mouse, speaker(s), etc. A power supply isprovided inside the housing 172 to provide power to the componentstherein requiring power. A cooling system, such as a fan, may also beprovided to cool the OSI device 170 from heat generating componentstherein.

The display 174 is driven by the control system to provide informationregarding a patient's imaged tear film, including TFLT. The display 174also provides a graphical user interface (GUI) to allow a clinician orother user to control the OSI device 170. To allow for human diagnosisof the patient's tear film, images of the patient's ocular tear filmtaken by the imaging device in the housing 172 can also be displayed onthe display 174 for review by a clinician, as will be illustrated anddescribed in more detail below. The images displayed on the display 174may be real-time images being taken by the imaging device, or may bepreviously recorded images stored in memory. To allow for differentorientations of the OSI device 170 to provide a universal configurationfor manufacturing, the display 174 can be rotated about the base 178.The display 174 is attached to a monitor arm 182 that is rotatable aboutthe base 178, as illustrated. The display 174 can be placed opposite ofthe patient head support 176, as illustrated in FIG. 9, if the cliniciandesires to sit directly across from the patient. Alternatively, thedisplay 174 can be rotated either left or right about the X-axis to beplaced adjacent to the patient head support 176. The display 174 may bea touch screen monitor to allow a clinician or other user to provideinput and control to the control system inside the housing 172 directlyvia touch of the display 174 for control of the OSI device 170. Thedisplay 174 illustrated in FIG. 9 is a fifteen inch (15″) flat panelliquid crystal display (LCD). However, the display 174 may be providedof any type or size, including but not limited to a cathode ray tube(CRT), plasma, LED, OLED, projection system, etc.

FIG. 10 illustrates a side view of the OSI device 170 of FIG. 9 tofurther illustrate imaging of a patient's eye and ocular tear film. Asillustrated therein, a patient 184 places their head in the patient headsupport 176. More particularly, the patient places their forehead 186against a headrest 188 provided as part of the patient head support 176.The patient places their chin 190 in the chin rest 180. The patient headsupport 176 is designed to facilitate alignment of a patient's 184 eye192 with the OSI device 170, and in particular, an imaging device 194(and the illuminator 173 with LEDS 196) shown as being provided insidethe housing 172. The chin rest 180 can be adjusted higher or lower tomove the patient's 184 eye 192 with respect to the OSI device 170.

As shown in FIG. 11, the imaging device 194 is used to image thepatient's ocular tear film to determine characteristics of the patient'stear film. In particular, the imaging device 194 is used to captureinterference interactions of the specularly reflected light 197 from thepatient's tear film when illuminated by the illuminator 173 (alsoreferred to herein as “illuminator 173”) as well as background signal.As previously discussed, background signal may be captured when theilluminator 173 is illuminating or not illuminating a patient's tearfilm. In the OSI device 170, the imaging device 194 is “The ImagingSource” model DFK21BU04 charge coupling device (CCD) digital videocamera 198, but many types of metrological grade cameras or imagingdevices can be provided. The CCD digital video camera 198 employs animaging lens 199 to focus the captured specularly reflected light 197onto a CCD chip (not shown). A CCD camera enjoys characteristics ofefficient light gathering, linear behavior, cooled operation, andimmediate image availability. A linear imaging device is one thatprovides an output signal representing a captured image which isprecisely proportional to the input signal from the captured image.Thus, use of a linear imaging device (e.g., gamma correction set to 1.0,or no gamma correction) provides undistorted interference data which canthen be analyzed using linear analysis models. In this manner, theresulting images of the tear film do not have to be linearized beforeanalysis, thus saving processing time. Gamma correction can then beadded to the captured linear images for human-perceptible display on anon-linear display 174 in the OSI device 170. Alternatively, theopposite scenario could be employed. That is, a non-linear imagingdevice or non-linear setting would be provided to capture tear filmimages, wherein the non-linear data representing the interferenceinteractions of the interference signal can be provided to a non-lineardisplay monitor without manipulation to display the tear film images toa clinician. The non-linear data would be linearized for tear filmprocessing and analysis to estimate tear film layer thickness.

The video camera 198 is capable of producing lossless full motion videoimages of the patient's eye. As illustrated in FIG. 11, the video camera198 has a depth of field defined by the angle between specularlyreflected light rays 197 and the lens focal length that allows thepatient's entire tear film to be in focus simultaneously. The videocamera 198 has an external trigger support so that the video camera 198can be controlled by a control system to image the patient's 184 eye192. The video camera 198 includes the imaging lens 199 that fits withinthe housing 172. The video camera 198 in this embodiment has aresolution of 640×480 pixels and is capable of frame rates up to sixty(60) frames per second (fps). The lens system employed in the videocamera 198 images a 16×12 mm dimension in a sample plane onto an activearea of a CCD detector within the video camera 198. As an example, thevideo camera 198 may be the DBK21AU04 Bayer VGA (640×480) video camerausing a Pentax VS-LD25 Daitron 25-mm fixed focal length lens. Othercamera models with alternate pixel size and number, alternate lenses,(etc.) may also be employed.

Although a video camera 198 is provided in the OSI device 170, a stillcamera could also be used if the frame rate is sufficiently fast enoughto produce high quality images of the patient's eye. High frame rate inframes per second (fps) facilitates high quality subtraction ofbackground signal from a captured interference signal representingspecularly reflected light from a patient's tear film, and may provideless temporal (i.e., motion) artifacts (e.g., motion blurring) incaptured images, resulting in high quality captured images. This isespecially the case since the patient's eye may move irregularly as wellas blinking, obscuring the tear film from the imaging device duringexamination.

A camera positioning system 200 is also provided in the housing 172 ofthe OSI device 170 to position the video camera 198 for imaging of thepatient's tear film. The camera positioning system 200 is under thecontrol of a control system. In this manner, a clinician can manipulatethe position of the video camera 198 to prepare the OSI device 170 toimage the patient's tear film. The camera positioning system 200 allowsa clinician and/or control system to move the video camera 198 betweeneach of the patient's 184 eyes 192, but can also be designed to limitthe range of motion within designed tolerances. The camera positioningsystem 200 also allows for fine tuning of the video camera 198 position.The camera positioning system 200 includes a stand 202 attached to abase 204. A linear servo or actuator 206 is provided in the camerapositioning system 200 and connected between the stand 202 and a cameraplatform 207 supporting the video camera 198 to allow the video camera198 to be moved in the vertical (i.e., Y-axis) direction.

In this embodiment of the OSI device 170, the camera positioning system200 may not allow the video camera 198 to be moved in the X-axis or theZ-axis (in and out of FIG. 11), but the disclosure is not so limited.The illuminator 173 is also attached to the camera platform 207 suchthat the illuminator 173 maintains a fixed geometric relationship to thevideo camera 198. Thus, when the video camera 198 is adjusted to thepatient's 184 eye 192, the illuminator 173 is automatically adjusted tothe patient's 184 eye 192 in the same regard as well. This may beimportant to enforce a desired distance (d) to properly capture theinterference interactions of the specularly reflected light from thepatient's tear film at the proper angle of incidence according toSnell's law, since the OSI device 170 is programmed to assume a certaindistance and certain angles of incidence.

In this exemplary embodiment, the Placido disk 175 is frusto-conicalshaped with an open major base and an open minor base with the openminor base facing the imaging device 194, while the open major basefaces the patient 184. The Placido disk 175 is centered about an opticalaxis 210 that extends between the patient's 184 eye 192 and the imaginglens 199. Moreover, a controller 209 controls the pixels of the Placidodisk 175 to generate a circular pattern, which is shown in thisexemplary embodiment as a circular tiled pattern 211. The circular tiledpattern 211 includes concentric circles 212 with alternating dark tiles213 and light tiles 214 that have edges that form radials 215. In atleast one embodiment, the pixels that generate the circular tiledpattern are liquid crystals such as those that make up a traditionalliquid crystal display (LCD). The liquid crystals are controllable toalign in a first direction to generate opaque pixels that make up thedark tiles 213. Alternately, the liquid crystals are controllable toalign in a second direction to generate translucent pixels that make upthe light tiles 214. In at least one other embodiment, pixels of thePlacido disk 175 are active devices such as OLEDs that can be controlledto emit multi-wavelength light in place of the illuminator 173.

Tear Film Thickness Measurement

A tear film thickness measurement using OSI device 170 is accomplishedby the procedure depicted in FIG. 6. In particular, a tear filmmeasurement is initiated by adjusting the patient's 184 eye 192 to theimaging device 194 (block 92). Next, a first circular pattern isprojected onto the eye 192 when illuminated by the illuminator 173(block 94). While illuminating the tear film 123 in the first mode, theimaging device 194 captures the first image 120 of the patient's eye 121and the tear film 123 as shown in FIG. 7A (block 96). The controller 209inverts the pixels after the projection of the first circular pattern inorder to project a second circular pattern onto the eye 192 whenilluminated by the illuminator 173 (block 98). In the exemplaryembodiment of the OSI device 170, the Placido disk 175 does not rotateto invert the first circular pattern to generate the second circularpattern. Instead, the controller 209 transitions the light pixels todark pixels and vice versa to invert the first circular pattern andthereby generate the second circular pattern. A second image 130 iscaptured of the tear film 123 is captured in the second mode, asillustrated by example in FIG. 7B (block 100, FIG. 6). It is to beunderstood that the controller 209 synchronizes the frequency ofalternating projections of the first circular pattern and the secondcircular pattern with the capturing of images via the imaging device194.

As shown in the second image 130 in FIG. 7B, the second portions 128A inthe first image 120 of FIG. 7A are now second portions 128B in thesecond image 130 in FIG. 7B containing specularly reflected light fromthe tear film 123 with additive background signal. The first portions126A in the first image 120 of FIG. 7A are now first portions 126B inthe second image 130 in FIG. 7B containing background signal withoutspecularly reflected light. Again, the background signal in the firstportions 126B includes scattered light signal as a result of diffuseillumination by the illuminator 173. The imaging device 194 produces asecond output signal of the second image 130 in FIG. 7B. The illuminator173 may also be flashed in block 98 to produce specularly reflectedlight from the second portions 128B, whereby the imaging device 194 issynchronized with the frequency of the projection of the second circularpattern in block 98 to capture the second image 130 of the patient's 184eye 192 and the tear film 123. The first and second output signals canthen be combined to produce a resulting signal comprised of theinterference signal of the specularly reflected light from the tear film123 with background signal subtracted or substantially removed from theinterference signal (block 102, FIG. 6). A resulting image is producedand displayed as a result of having interference information from thespecularly reflected light from the tear film 123 with background signaleliminated or reduced, including background signal resulting fromscattered light from diffuse illumination by the illuminator 173 (block104, FIG. 6). An example of a resulting image 132 in this regard isillustrated in FIG. 7C. The resulting image 132 represents the firstoutput signal represented by the first image 120 in FIG. 7A combinedwith the second output signal represented by the second image 130 inFIG. 7B. As illustrated in FIG. 7C, interference signals of specularlyreflected light from the tear film 123 are provided for both the firstand second portions 126, 128 of the tear film 123. The background signalhas been eliminated or reduced. In this manner, a medical doctor is ableto have a visualization of the patient's 184 tear film 123.

Corneal Topography

Beyond tear film measurement, the OSI device 170 is ideal for conductingcorneal topography mapping. A flowchart depicting a process for cornealtopography mapping using the OSI device 170 is shown in FIG. 12. Thecorneal topography mapping process is initiated by adjusting thepatient's 184 eye 192 to the imaging device 194 (block 216). Once properadjustments are made, the patient's 184 eye 192 is illuminated via theilluminator 173 and a first circular pattern is projected onto the eye192 before acquiring a corneal topography mapping image (block 217).Once the eye 192 is illuminated, a first image(s) of the eye 192 iscaptured with the first circular pattern reflected from the eye 192(block 218). After capturing the first image(s) the first circularpattern is inverted to provide a second circular pattern that isprojected onto the eye 192 (block 219). Next, a second image(s) of theeye 192 with the second circular pattern reflecting therefrom iscaptured by the imaging device 194 (block 220). The OSI device 170 thencombines the first image(s) and the second image(s) to provide a thirdcircular pattern containing corneal topography information (block 221).Lastly, the third circular pattern containing the corneal topographyinformation is displayed on the display 174 (block 222). FIG. 13 depictsan example of a third circular pattern 223 containing an indication of acorneal aberration 224 that is visually represented as a bump in aradial 215.

FIGS. 14 and 15 are prior art figures from U.S. Pat. No. 6,450,641 toD'Souza et al (hereafter D'Souza). In particular, D'Souza is directed toa method of corneal analysis using a checkered Placido apparatus. FIG.14 is a rearview of the D'Souza checkered Placido disk and FIG. 15 is aside view of the D'Souza checkered Placido image projected onto acornea. While FIG. 14 depicts a pattern similar to the present circularpattern 211 (FIG. 11), the D'Souza checkered Placido disk is not usablefor measuring tear film thickness. For example, the D'Souza checkeredPlacido disk does not have a means for projecting a first circularpattern onto a cornea, inverting the first circular pattern to generatea second circular pattern and then projecting the second circularpattern onto the cornea like the OSI devices of the present disclosure.In other words, D'Souza does not rotate the checkered Placido disk orinvert pixels so that dark areas and light areas are swapped between afirst circular checkered pattern and a second circular checkeredpattern. Further still, D'Souza does not combine a first image(s) of afirst circular pattern reflected from a cornea with a second image(s) ofa second circular pattern reflected from the cornea to generate a thirdcircular pattern without tiles (i.e. no checkered pattern). As a result,D'Souza does not teach or suggest tear film thickness measurement. Inparticular, D'Souza does not include the color processing of the presentembodiments that relate color to light specularly reflected from thetear film that undergo constructive and destructive optical waveinterference interactions. Thus, D'Souza does not teach or suggest thecombined tear film measurement and corneal topography mapping OSI deviceembodiments of the present disclosure.

Combined Tear Film Measurement and Corneal Topography

Since the OSI device embodiments of the present disclosure provide morearea of tear film 123 than with traditional tear film measurementinstruments and techniques, it may be important to understand if thereare tear film deficiencies located at corneal aberrations such as scartissue. As such, a medical doctor may need to visually inspect theresultant image containing both tear film measurement informationcombined with corneal topography information. The OSI device 170 can becontrolled by the medical doctor to display an image of both the tearfilm along with corneal topography mapping information. Therefore, notonly can the medical doctor use the resultant image to examine the RGBcolor representations of the lipid layer, the medical doctor is now alsoable to visually correlate abnormalities in lipid layer thickness withabnormalities in the corneal shape of the eye.

In this regard, FIG. 16 is a flowchart of an exemplary process ofmeasuring tear film thickness combined with corneal topography mappingusing the OSI device 30 of FIGS. 4A and 4B or the OSI device 170 ofFIGS. 9-11. The exemplary process for conducting a tear film measurementcombined with corneal topography mapping is initiated by adjusting thepatient's 184 eye 192 to the imaging device 194 (block 225). Once thepatient's 184 eye 192 is adjusted to the imaging device 194, the tearfilm is illuminated by the illuminator 173 and a first circular patternis projected onto the tear film to produce specularly reflected lightfrom first portion(s) in the tear film while non-specularly illuminatingsecond adjacent portion(s) of the tear film (block 226). Next, theimaging device 194 captures a first image(s) of the eye 192 with thefirst circular pattern reflecting from the eye along with the specularlight reflections from the tear film (block 227). Once the firstimage(s) are captured, the first circular pattern is inverted to providea second circular pattern (block 228). Next, a second image(s) of theeye 192 is captured while the second circular pattern is reflecting fromthe eye 192 along with the specular reflection from the tear film (block229). Afterwards, the first image(s) and the second image(s) arecombined to provide a third circular pattern containing both cornealtopography and tear film thickness information (block 230). Lastly, thethird circular pattern containing the corneal topography information andthe tear film information is displayed on the display 174 (block 231).

System Level

Now that the imaging and illumination functions of the OSI device 170have been described, FIG. 17A illustrates a system level diagramillustrating more detail regarding the control system and other internalcomponents of the OSI device 170 provided inside the housing 172according to one embodiment to capture images of a patient's tear filmand process those images. As illustrated therein, a control system 240is provided for the overall control of the OSI device 170. The controlsystem 240 may be provided by any microprocessor-based or computersystem. The control system 240 illustrated in FIG. 17A is provided in asystem-level diagram and does not necessarily imply a specific hardwareorganization and/or structure. As illustrated therein, the controlsystem 240 contains several systems. A camera settings system 242 may beprovided that accepts camera settings from a clinician user. Exemplarycamera settings 244 are illustrated, but may be any type according tothe type and model of camera provided in the OSI device 170 as is wellunderstood by one of ordinary skill in the art.

The camera settings 244 may be provided to (The Imaging Source) cameradrivers 246, which may then be loaded into the video camera 198 uponinitialization of the OSI device 170 for controlling the settings of thevideo camera 198. The settings and drivers may be provided to a buffer248 located inside the video camera 198 to store the settings forcontrolling a CCD 250 for capturing ocular image information from a lens252. Ocular images captured by the lens 252 and the CCD 250 are providedto a de-Bayering function 254 which contains an algorithm forpost-processing of raw data from the CCD 250 as is well known. Theocular images are then provided to a video acquisition system 256 in thecontrol system 240 and stored in memory, such as random access memory(RAM) 258. The stored ocular images or signal representations can thenbe provided to a pre-processing system 260 and a post-processing system262 to manipulate the ocular images to obtain the interferenceinteractions of the specularly reflected light from the tear film andanalyze the information to determine characteristics of the tear film.Pre-processing settings 264 and post-processing settings 266 can beprovided to the pre-processing system 260 and post-processing system262, respectively, to control these functions. These settings 264, 266will be described in more detail below. The post-processed ocular imagesand information may also be stored in mass storage, such as disk memory268, for later retrieval and viewing on the display 174.

The control system 240 may also contain a visualization system 270 thatprovides the ocular images to the display 174 to be displayed inhuman-perceptible form on the display 174. Before being displayed, theocular images may have to be pre-processed in a pre-processing videofunction 272. For example, if the ocular images are provided by a linearcamera, non-linearity (i.e. gamma correction) may have to be added inorder for the ocular images to be properly displayed on the display 174.Further, contrast and saturation display settings 274, which may becontrolled via the display 174 or a device communicating to the display174, may be provided by a clinician user to control the visualization ofocular images displayed on the display 174. The display 174 is alsoadapted to display analysis result information 276 regarding thepatient's tear film, as will be described in more detail below. Thecontrol system 240 may also contain a user interface system 278 thatdrives a graphical user interface (GUI) utility 280 on the display 174to receive user input 282. The user input 282 can include any of thesettings for the OSI device 170, including the camera settings 244, thepre-processing settings 264, the post-processing settings 266, thedisplay settings 274, the visualization system 270 enablement, and videoacquisition system 256 enablement, labeled 1-6. The GUI utility 280 mayonly be accessible by authorized personnel and used for calibration orsettings that would normally not be changed during normal operation ofthe OSI device 170 once configured and calibrated.

Overall Process Flow

FIG. 17B illustrates an exemplary overall flow process performed by theOSI device 170 for capturing tear film images from a patient andanalysis for TFLT measurement. As illustrated in FIG. 17B, the videocamera 198 is connected via a USB port 283 to the control system 240(see FIG. 17A) for control of the video camera 198 and for transferringimages of a patient's tear film taken by the video camera 198 back tothe control system 240. The control system 240 includes a compatiblecamera driver 246 to provide a transfer interface between the controlsystem 240 and the video camera 198. Prior to tear film image capture,the configuration of camera settings 244 is loaded into the video camera198 over the USB port 283 to prepare the video camera 198 for tear filmimage capture (block 285). Further, an audio video interleaved (AVI)container is created by the control system 240 to store video of tearfilm images to be captured by the video camera 198 (block 286). At thispoint, the video camera 198 and control system 240 are ready to captureimages of a patient's tear film. The control system 240 waits for a usercommand to initiate capture of a patient's tear film (blocks 287, 288).

Once image capture is initiated (block 288), the control system 240enables image capture to the AVI container previously setup (block 286)for storage of images captured by the video camera 198 (block 289). Thecontrol system 240 controls the video camera 198 to capture images ofthe patient's tear film (block 289) until timeout or the user terminatesimage capture (block 290) and image capture halts or ends (block 291).Images captured by the video camera 198 and provided to the controlsystem 240 over the USB port 283 are stored by the control system 240 inRAM 258.

The captured images of the patient's ocular tear film can subsequentlybe processed and analyzed to perform TFLT measurement, as described inmore detail below and throughout the remainder of this disclosure. Theprocess in this embodiment involves processing tear film image pairs toperform background subtraction, as previously discussed. For example,image tiling may be performed to provide the tear film image pairs, ifdesired. The processing can include simply displaying the patient's tearfilm or performing TFLT measurement (block 293). If the display optionis selected to allow a technician to visually view the patient's tearfilm, display processing is performed (block 294) which can be thevisualization system 270 described in more detail below with regard toFIG. 26. For example, the control system 240 can provide a combinationof images of the patient's tear film that show the entire region ofinterest of the tear film on the display 174. The displayed image mayinclude the background signal or may have the background signalsubtracted. If TFLT measurement is desired, the control system 240performs pre-processing of the tear film images for TFLT measurement(block 295), which can be the pre-processing system 260 described inmore detail below with regard to FIG. 18. The control system 240 alsoperforms post-processing of the tear film images for TFLT measurement(block 296), which can be the post-processing system 262 described inmore detail below with regard to FIG. 28.

Pre-Processing

FIG. 18 illustrates an exemplary pre-processing system 260 forpre-processing ocular tear film images captured by the OSI device 170for eventual analysis and TFLT measurement. In this system, the videocamera 198 has already taken the first and second tiled images of apatient's ocular tear film, as previously illustrated in FIGS. 11A and11B, and provided the images to the video acquisition system 256. Theframes of the first and second images were then loaded into RAM 258 bythe video acquisition system 256. Thereafter, as illustrated in FIG. 18,the control system 240 commands the pre-processing system 260 topre-process the first and second images. An exemplary GUI utility 280 isillustrated in FIG. 19 that may be employed by the control system 240 toallow a clinician to operate the OSI device 170 and controlpre-processing settings 264 and post-processing settings 266, which willbe described later in this application. In this regard, thepre-processing system 260 loads the first and second image frames of theocular tear film from RAM 258 (block 300). The exemplary GUI utility 280in FIG. 19 allows for a stored image file of previously stored videosequence of first and second image frames captured by the video camera198 by entering a file name in the file name field 351. A browse button352 also allows searches of the memory for different video files, whichcan either be buffered by selecting a buffer box 354 or loaded forpre-processing by selecting the load button 356.

If the loaded first and second image frames of the tear film arebuffered, they can be played using display selection buttons 358, whichwill in turn display the images on the display 174. The images can beplayed on the display 174 in a looping fashion, if desired, by selectingthe loop video selection box 360. A show subtracted video selection box370 in the GUI utility 280 allows a clinician to show the resulting,subtracted video images of the tear film on the display 174representative of the resulting signal comprised of the second outputsignal combined or subtracted from the first output signal, or viceversa. Also, by loading the first and second image frames, thepreviously described subtraction technique can be used to removebackground image from the interference signal representing interferenceof the specularly reflected light from the tear film, as previouslydescribed above and illustrated in FIG. 12 as an example. The firstimage is subtracted from the second image to subtract or remove thebackground signal in the portions producing specularly reflected lightin the second image, and vice versa, and then combined to produce aninterference interaction of the specularly reflected light of the entirearea or region of interest of the tear film, as previously illustratedin FIG. 12 (block 302 in FIG. 18). For example, this processing could beperformed using the Matlab® function “cvAbsDiff.”

The subtracted image containing the specularly reflected light from thetear film can also be overlaid on top of the original image capture ofthe tear film to display an image of the entire eye and the subtractedimage in the display 174 by selecting the show overlaid original videoselection box 362 in the GUI utility 280 of FIG. 19. An example of anoverlaid original video to the subtracted image of specularly reflectedlight from the tear film is illustrated in the image 363 of FIG. 20.This overlay is provided so that flashing images of specularly reflectedlight from the tear film are not displayed, which may be unpleasant tovisualize. An image, such as image 363 of the tear film illustrated inFIG. 20 may be obtained with a DBK 21AU04 Bayer VGA (640×480) videocamera having a Pentax VS-LD25 Daitron 25-mm fixed focal length lenswith maximum aperture at a working distance of 120 mm and having thefollowing settings, as an example:

-   -   Gamma=100 (to provide linearity with exposure value)    -   Exposure= 1/16 second    -   Frame rate=60 fps    -   Data Format=BY8    -   Video Format=-uncompressed, RGB 24-bit AVI    -   Hue=180 (neutral, no manipulation)    -   Saturation=128 (neutral, no manipulation)    -   Brightness=0 (neutral, no manipulation)    -   Gain=260 (minimum available setting in this camera driver)    -   White balance=B=78; R=20.        Thresholding

Any number of optional pre-processing steps and functions can next beperformed on the resulting combined tear film image(s), which will nowbe described. For example, an optional threshold pre-processing functionmay be applied to the resulting image or each image in a video of imagesof the tear film (e.g., FIG. 12) to eliminate pixels that have asubtraction difference signal below a threshold level (block 304 in FIG.18). Image threshold provides a black and white mask (on/off) that isapplied to the tear film image being processed to assist in removingresidual information that may not be significant enough to be analyzedand/or may contribute to inaccuracies in analysis of the tear film. Thethreshold value used may be provided as part of a threshold valuesetting provided by a clinician as part of the pre-processing settings264, as illustrated in the system diagram of FIG. 17A. For example, theGUI utility 280 in FIG. 19 includes a compute threshold selection box372 that may be selected to perform thresholding, where the thresholdbrightness level can be selected via the threshold value slide 374. Thecombined tear film image of FIG. 12 is copied and converted tograyscale. The grayscale image has a threshold applied according to thethreshold setting to obtain a binary (black/white) image that will beused to mask the combined tear film image of FIG. 12. After the mask isapplied to the combined tear film image of FIG. 12, the new combinedtear film image is stored in RAM 258. The areas of the tear film imagethat do not meet the threshold brightness level are converted to blackas a result of the threshold mask.

FIGS. 21A and 21B illustrate examples of threshold masks for thecombined tear film provided in FIG. 12. FIG. 21A illustrates a thresholdmask 320 for a threshold setting of 70 counts out of a full scale levelof 255 counts. FIG. 21B illustrates a threshold mask 322 for a thresholdsetting of 50. Note that the threshold mask 320 in FIG. 21A containsless portions of the combined tear film image, because the thresholdsetting is higher than for the threshold mask 322 of FIG. 21B. When thethreshold mask according to a threshold setting of 70 is applied to theexemplary combined tear film image of FIG. 12, the resulting tear filmimage is illustrated FIG. 22. Much of the residual subtracted backgroundimage that surrounds the area or region of interest has been maskedaway.

Erode and Dilate

Another optional pre-processing function that may be applied to theresulting image or each image in a video of images of the tear film tocorrect anomalies in the combined tear film image(s) is the erode anddilate functions (block 306 in FIG. 18). The erode function generallyremoves small anomaly artifacts by subtracting objects with a radiussmaller than an erode setting (which is typically in number of pixels)removing perimeter pixels where interference information may not be asdistinct or accurate. The erode function may be selected by a clinicianin the GUI utility 280 (see FIG. 19) by selecting the erode selectionbox 376. If selected, the number of pixels for erode can be provided inan erode pixels text box 378. Dilating generally connects areas that areseparated by spaces smaller than a minimum dilate size setting by addingpixels of the eroded pixel data values to the perimeter of each imageobject remaining after the erode function is applied. The dilatefunction may be selected by a clinician in the GUI utility 280 (see FIG.19) by providing the number of pixels for dilating in a dilate pixelstext box 380. Erode and dilate can be used to remove small regionanomalies in the resulting tear film image prior to analyzing theinterference interactions to reduce or avoid inaccuracies. Theinaccuracies may include those caused by bad pixels of the video camera198 or from dust that may get onto a scanned image, or more commonly,spurious specular reflections such as: tear film meniscus at thejuncture of the eyelids, glossy eyelash glints, wet skin tissue, etc.FIG. 23 illustrates the resulting tear film image of FIG. 22 after erodeand dilate functions have been applied and the resulting tear film imageis stored in RAM 258. As illustrated therein, pixels previously includedin the tear film image that were not in the tear film area or region ofinterest are removed. This prevents data in the image outside the areaor region of interest from affecting the analysis of the resulting tearfilm image(s).

Removing Blinks/Other Anomalies

Another optional pre-processing function that may be applied to theresulting image or each image in a video of images of the tear film tocorrect anomalies in the resulting tear film image is to remove framesfrom the resulting tear film image that include patient blinks orsignificant eye movements (block 308 in FIG. 18). As illustrated in FIG.18, blink detection is shown as being performed after a threshold anderode and dilate functions are performed on the tear film image or videoof images. Alternatively, the blink detection could be performedimmediately after background subtraction, such that if a blink isdetected in a given frame or frames, the image in such frame or framescan be discarded and not pre-processed. Not pre-processing images whereblinks are detected may increase the overall speed of pre-processing.The remove blinks or movement pre-processing may be selectable. Forexample, the GUI utility 280 in FIG. 19 includes a remove blinksselection box 384 to allow a user to control whether blinks and/or eyemovements are removed from a resulting image or frames of the patient'stear film prior to analysis. Blinking of the eyelids covers the oculartear film, and thus does not produce interference signals representingspecularly reflected light from the tear film. If frames containingwhole or partial blinks obscuring the area or region of interest in thepatient's tear film are not removed, it would introduce errors in theanalysis of the interference signals to determine characteristics of theTFLT of the patient's ocular tear film. Further, frames or data withsignificant eye movement between sequential images or frames can beremoved during the detect blink pre-processing function. Large eyemovements could cause inaccuracy in analysis of a patient's tear filmwhen employing subtraction techniques to remove background signal,because subtraction involves subtracting frame-pairs in an image thatclosely match spatially. Thus, if there is significant eye movementbetween first and second images that are to be subtracted, frame pairsmay not be closely matched spatially thus inaccurately removingbackground signal, and possibly removing a portion of the interferenceimage of specularly reflected light from the tear film.

Different techniques can be used to determine blinks in an ocular tearfilm image and remove the frames as a result. For example, in oneembodiment, the control system 240 directs the pre-processing system 260to review the stored frames of the resulting images of the tear film tomonitor for the presence of an eye pupil using pattern recognition. AHough Circle Transform may be used to detect the presence of the eyepupil in a given image or frame. If the eye pupil is not detected, it isassembled such that the image or frame contains an eye blink and thusshould be removed or ignored during pre-processing from the resultingimage or video of images of the tear film. The resulting image or videoof images can be stored in RAM 258 for subsequent processing and/oranalyzation.

In another embodiment, blinks and significant eye movements are detectedusing a histogram sum of the intensity of pixels in a resultingsubtracted image or frame of a first and second image of the tear film.An example of such a histogram 329 is illustrated in FIG. 24. Theresulting or subtracted image can be converted to grayscale (i.e., 255levels) and a histogram generated with the gray levels of the pixels. Inthe histogram 329 of FIG. 24, the x-axis contains gray level ranges, andthe number of pixels falling within each gray level is contained in they-axis. The total of all the histogram 329 bins are summed. In the caseof two identical frames that are subtracted, the histogram sum would bezero. However, even without an eye blink or significant eye movement,two sequentially captured frames of the patient's eye and theinterference signals representing the specularly reflected light fromthe tear film are not identical. However, frame pairs with littlemovement will have a low histogram sum, while frame pairs with greatermovement will yield a larger histogram sum. If the histogram sum isbeyond a pre-determined threshold, an eye blink or large eye movementcan be assumed and the image or frame removed. For example, the GUIutility 280 illustrated in FIG. 19 includes a histogram sum slide bar386 that allows a user to set the threshold histogram sum. The thresholdhistogram sum for determining whether a blink or large eye movementshould be assumed and thus the image removes from analysis of thepatient's tear film can be determined experimentally, or adaptively overthe course of a frame playback, assuming that blinks occur at regularintervals.

An advantage of a histogram sum of intensity method to detect eye blinksor significant eye movements is that the calculations are highlyoptimized as opposed to pixel-by-pixel analysis, thus assisting withreal-time processing capability. Further, there is no need to understandthe image structure of the patient's eye, such as the pupil or the irisdetails. Further, the method can detect both blinks and eye movements.

Another alternate technique to detect blinks in the tear film image orvideo of images for possible removal is to calculate a simple averagegray level in an image or video of images. Because the subtracted,resulting images of the tear film subtract background signal, and havebeen processed using a threshold mask, and erode and dilate functionsperformed in this example, the resulting images will have a loweraverage gray level due to black areas present than if a blink ispresent. A blink contains skin color, which will increase the averagegray level of an image containing a blink. A threshold average graylevel setting can be provided. If the average gray level of a particularframe is below the threshold, the frame is ignored from further analysisor removed from the resulting video of frames of the tear film.

Another alternate technique to detect blinks in an image or video ofimages for removal is to calculate the average number of pixels in agiven frame that have a gray level value below a threshold gray levelvalue. If the percentage of pixels in a given frame is below a definedthreshold percentage, this can be an indication that a blink hasoccurred in the frame, or that the frame is otherwise unworthy ofconsideration when analyzing the tear film. Alternatively, a spatialfrequency calculation can be performed on a frame to determine theamount of fine detail in a given frame. If the detail present is below athreshold detail level, this may be an indication of a blink or otherobscurity of the tear film, since skin from the eyelid coming down andbeing captured in a frame will have less detail than the subtractedimage of the tear film. A histogram can be used to record any of theabove-referenced calculations to use in analyzing whether a given frameshould be removed from the final pre-processed resulting image or imagesof the tear film for analyzation.

ICC Profiling

Pre-processing of the resulting tear film image(s) may also optionallyinclude applying an International Colour Consortium (ICC) profile to thepre-processed interference images of the tear film (block 310, FIG. 18).FIG. 25 illustrates an optional process of loading an ICC profile intoan ICC profile 331 in the control system 240 (block 330). In thisregard, the GUI utility 280 illustrated in FIG. 19 also includes anapply ICC box 392 that can be selected by a clinician to load the ICCprofile 331. The ICC profile 331 may be stored in memory in the controlsystem 240, including in RAM 258. In this manner, the GUI utility 280 inFIG. 19 also allows for a particular ICC profile 331 to be selected forapplication in the ICC profile file text box 394. The ICC profile 331can be used to adjust color reproduction from scanned images fromcameras or other devices into a standard red-green-blue (RGB) colorspace (among other selectable standard color spaces) defined by the ICCand based on a measurement system defined internationally by theCommission Internationale de l'Eclairage (CIE). Adjusting thepre-processed resulting tear film interference images corrects forvariations in the camera color response and the light source spectrumand allows the images to be compatibly compared with a tear film layerinterference model to measure the thickness of a TFLT, as will bedescribed later in this application. The tear film layers represented inthe tear film layer interference model can be LLTs, ALTs, or both, aswill be described in more detail below.

In this regard, the ICC profile 331 may have been previously loaded tothe OSI device 170 before imaging of a patient's tear film and alsoapplied to a tear film layer interference model when loaded into the OSIdevice 170 independent of imaging operations and flow. As will bediscussed in more detail below, a tear film layer interference model inthe form of a TFLT palette 333 containing color values representinginterference interactions from specularly reflected light from a tearfilm for various LLTs and ALTs can also be loaded into the OSI device170 (block 332 in FIG. 25). The TFLT palette 333 contains a series ofcolor values that are assigned LLTs and/or ALTs based on a theoreticaltear film layer interference model to be compared against the colorvalue representations of interference interactions in the resultingimage(s) of the patient's tear film. When applying the optional ICCprofile 331 to the TFLT palette 333 (block 334 in FIG. 25), the colorvalues in both the tear film layer interference model and the colorvalues representing interference interactions in the resulting image ofthe tear film are adjusted for a more accurate comparison between thetwo to measure LLT and/or ALT.

Brightness

Also as an optional pre-processing step, brightness and red-green-blue(RGB) subtract functions may be applied to the resulting interferencesignals of the patient's tear film before post-processing for analysisand measuring TFLT is performed (blocks 312 and 314 respectively in FIG.18). The brightness may be adjusted pixel-by-pixel by selecting theadjust brightness selection box 404 according to a correspondingbrightness level value provided in a brightness value box 406, asillustrated in the GUI utility 280 of FIG. 19. When the brightness valuebox 406 is selected, the brightness of each palette value of the TFLTpalette 333 is also adjusted accordingly.

RGB Subtraction (Normalization)

The RGB subtract function subtracts a DC offset from the interferencesignal in the resulting image(s) of the tear film representing theinterference interactions in the interference signal. An RGB subtractsetting may be provided from the pre-processing settings 264 to apply tothe interference signal in the resulting image of the tear film tonormalize against. As an example, the GUI utility 280 in FIG. 19 allowsan RGB offset to be supplied by a clinician or other technician for usein the RGB subtract function. As illustrated therein, the subtract RGBfunction can be activated by selecting the RGB subtract selection box396. If selected, the individual RGB offsets can be provided in offsetvalue input boxes 398. After pre-processing is performed, if any, on theresulting image, the resulting image can be provided to apost-processing system 262 to measure TLFT (block 316), as discussedlater below in this application.

Displaying Images

The resulting images of the tear film may also be displayed on thedisplay 174 of the OSI device 170 for human diagnosis of the patient'socular tear film. The OSI device 170 is configured so that a cliniciancan display and see the raw captured image of the patient's 184 eye 192by the video camera 198, the resulting images of the tear film beforepre-processing, or the resulting images of the tear film afterpre-processing. Displaying images of the tear film on the display 174may entail different settings and steps. For example, if the videocamera 198 provides linear images of the patient's tear film, the linearimages must be converted into a non-linear format to be properlydisplayed on the display 174. In this regard, a process that isperformed by the visualization system 270 according to one embodiment isillustrated in FIG. 26.

As illustrated in FIG. 26, the video camera 198 has already taken thefirst and second tiled images of a patient's ocular tear film aspreviously illustrated in FIGS. 11A and 11B, and provided the images tothe video acquisition system 256. The frames of the first and secondimages were then loaded into RAM 258 by the video acquisition system256. Thereafter, as illustrated in FIG. 26, the control system 240commands the visualization system 270 to process the first and secondimages to prepare them for being displayed on the display 174. In thisregard, the visualization system 270 loads the first and second imageframes of the ocular tear film from RAM 258 (block 335). The previouslydescribed subtraction technique is used to remove background signal fromthe interference interactions of the specularly reflected light from thetear film, as previously described above and illustrated in FIG. 12. Thefirst image(s) is subtracted from the second image(s) to removebackground signal in the illuminated portions of the first image(s), andvice versa, and the subtracted images are then combined to produce aninterference interaction of the specularly reflected light of the entirearea or region of interest of the tear film, as previously discussed andillustrated in FIG. 12 (block 336 in FIG. 26).

Again, for example, this processing could be performed using the Matlab®function “cvAbsDiff.” Before being displayed, the contrast andsaturation levels for the resulting images can be adjusted according tocontrast and saturation settings provided by a clinician via the userinterface system 278 and/or programmed into the visualization system 270(block 337). For example, the GUI utility 280 in FIG. 19 provides anapply contrast button 364 and a contrast setting slide 366 to allow theclinician to set the contrast setting in the display settings 274 fordisplay of images on the display 174. The GUI utility 280 also providesan apply saturation button 368 and a saturation setting slide 369 toallow a clinician to set the saturation setting in the display settings274 for the display of images on the display 174. The images can then beprovided by the visualization system 270 to the display 174 for viewing(block 338 in FIG. 26). Also, any of the resulting images afterpre-processing steps in the pre-processing system 260 can be provided tothe display 174 for processing.

FIGS. 27A-27C illustrate examples of different tear film images that aredisplayed on the display 174 of the OSI device 170. FIG. 27A illustratesa first image 339 of the patient's tear film showing the tiled patterncaptured by the video camera 198. This image is the same image asillustrated in FIG. 11A and previously described above, but processedfrom a linear output from the video camera 198 to be properly displayedon the display 174. FIG. 27B illustrates a second image 340 of thepatient's tear film illustrated in FIG. 11B and previously describedabove. FIG. 27C illustrates a resulting “overlaid” image 341 of thefirst and second images 339, 340 of the patient's tear film and toprovide interference interactions of the specularly reflected light fromthe tear film over the entire area or region of interest. This is thesame image as illustrated in FIG. 7C and previously described above.

In this example, the original number of frames of the patient's tearfilm captured can be reduced by half due to the combination of the firstand second tiled pattern image(s). Further, if frames in the subtractedimage frames capture blinks or erratic movements, and these frames areeliminated in pre-processing, a further reduction in frames will occurduring pre-processing from the number of images raw captured in imagesof the patient's tear film. Although these frames are eliminated frombeing further processed, they can be retained for visualization,rendering a realistic and natural video playback. Further, by applying athresholding function and erode and dilating functions, the number ofnon-black pixels which contain TLFT interference information issubstantially reduced as well. Thus, the amount of pixel informationthat is processed by the post-processing system 262 is reduced, and maybe on the order of 70 percent (%) less information to process than theraw image capture information, thereby pre-filtering for the desiredinterference ROI and reducing or eliminating potentially erroneousinformation as well as allowing for faster analysis due to the reductionin information.

At this point, the resulting images of the tear film have beenpre-processed by the pre-processing system 260 according to whateverpre-processing settings 264 and pre-processing steps have been selectedor implemented by the control system 240. The resulting images of thetear film are ready to be processed for analyzing and determining TFLT.In this example, this is performed by the post-processing system 262 inFIG. 17A and is based on the post-processing settings 266 alsoillustrated therein. An embodiment of the post-processing performed bythe post-processing system 262 is illustrated in the flowchart of FIG.28.

Tear Film Interference Models

As illustrated in FIG. 28, pre-processed images 343 of the resultingimages of the tear film are retrieved from RAM 258 where they werepreviously stored by the pre-processing system 260. Before discussingthe particular embodiment of the post-processing system 262 in FIG. 28,in general, to measure TFLT, the RGB color values of the pixels in theresulting images of the tear film are compared against color valuesstored in a tear film interference model that has been previously loadedinto the OSI device 170 (see FIG. 25). The tear film interference modelmay be stored as a TFLT palette 333 containing RGB values representinginterference colors for given LLTs and/or ALTs. The TFLT palettecontains interference color values that represent TFLTs based on atheoretical tear film interference model in this embodiment. Dependingon the TFLT palette 333 provided, the interference color valuesrepresented therein may represent LLTs, ALTs, or both. An estimation ofTFLT for each ROI pixel is based on this comparison. This estimate ofTFLT is then provided to the clinician via the display 174 and/orrecorded in memory to assist in diagnosing DES.

Before discussing embodiments of how the TFLTs are estimated from thepre-processed resulting image colored interference interactionsresulting from specularly reflected light from the tear film, tear filminterference modeling is first discussed. Tear film interferencemodeling can be used to determine an interference color value for agiven TFLT to measure TFLT, which can include both LLT and/or ALT.

Although the interference signals representing specularly reflectedlight from the tear film are influenced by all layers in the tear film,the analysis of interference interactions due to the specularlyreflected light can be analyzed under a 2-wave tear film model (i.e.,two reflections) to measure LLT. A 2-wave tear film model is based on afirst light wave(s) specularly reflecting from the air-to-lipid layertransition of a tear film and a second light wave specularly reflectingfrom the lipid layer-to-aqueous layer transition of the tear film. Inthe 2-wave model, the aqueous layer is effective ignored and treated tobe of infinite thickness. To measure LLT using a 2-wave model, a 2-wavetear film model was developed wherein the light source and lipid layersof varying thicknesses were modeled mathematically. To model thetear-film interference portion, commercially available software, such asthat available by FilmStar and Zemax as examples, allows imagesimulation of thin films for modeling. Relevant effects that can beconsidered in the simulation include refraction, reflection, phasedifference, polarization, angle of incidence, and refractive indexwavelength dispersion. For example, a lipid layer could be modeled ashaving an index of refraction of 1.48 or as a fused silica substrate(SiO₂) having a 1.46 index of refraction. A back material, such asMagnesium Flouride (MgF₂) having an index of refraction of 1.38, may beused to provide a 2-wave model of air/SiO₂/MgF₂ (1.0/1.46/1.38). Toobtain the most accurate modeling results, the model can include therefractive index and wavelength dispersion values of biological lipidmaterial and biological aqueous material, found from the literature,thus to provide a precise two-wave model of air/lipid/aqueous layers.Thus, a 2-wave tear film interference model allows measurement of LLTregardless of ALT.

Simulations can be mathematically performed by varying the LLT between10 to 300 nm. As a second step, the RGB color values of the resultinginterference signals from the modeled light source causing the modeledlipid layer to specularly reflect light and be received by the modeledcamera were determined for each of the modeled LLT. These RGB colorvalues representing interference interactions in specularly reflectedlight from the modeled tear film were used to form a 2-wave model LLTpalette, wherein each RGB color value is assigned a different LLT. Theresulting subtracted image of the first and second images from thepatient's tear film containing interference signals representingspecularly reflected light are compared to the RGB color values in the2-wave model LLT palette to measure LLT.

In another embodiment, a 3-wave tear film interference model may beemployed to estimate LLT. A 3-wave tear film interference model does notassume that the aqueous layer is infinite in thickness. In an actualpatient's tear film, the aqueous layer is not infinite. The 3-wave tearfilm interference model is based on both the first and second reflectedlight waves of the 2-wave model and additionally light wave(s)specularly reflecting from the aqueous-to-mucin layer and/or corneatransitions. Thus, a 3-wave tear film interference model recognizes thecontribution of specularly reflected light from the aqueous-to-mucinlayer and/or cornea transition that the 2-wave tear film interferencemodel does not. To estimate LLT using a 3-wave tear film interferencemodel, a 3-wave tear film model was previously constructed wherein thelight source and a tear film of varying lipid and aqueous layerthicknesses were mathematically modeled. For example, a lipid layercould be mathematically modeled as a material having an index ofrefraction of 1.48 or as fused silica substrate (SiO₂), which has a 1.46index of refraction. Different thicknesses of the lipid layer can besimulated. A fixed thickness aqueous layer (e.g., >=2 μm) could bemathematically modeled as Magnesium Flouride (MgF₂) having an index ofrefraction of 1.38. A biological cornea could be mathematically modeledas fused silica with no dispersion, thereby resulting in a 3-wave modelof air/SiO₂/MgF₂/SiO₂ (i.e., 1.0/1.46/1.38/1.46 with no dispersion). Asbefore, accurate results are obtained if the model can include therefractive index and wavelength dispersion values of biological lipidmaterial, biological aqueous material, and cornea tissue, found from theliterature, thus to provide a precise two-wave model ofair/lipid/aqueous/cornea layers. The resulting interference interactionsof specularly reflected light from the various LLT values and with afixed ALT value are recorded in the model and, when combined withmodeling of the light source and the camera, will be used to compareagainst interference from specularly reflected light from an actual tearfilm to measure LLT and/or ALT.

In another embodiment of the OSI device 170 and the post-processingsystem 262 in particular, a 3-wave tear film interference model isemployed to estimate both LLT and ALT. In this regard, instead ofproviding either a 2-wave theoretical tear film interference model thatassumes an infinite aqueous layer thickness or a 3-wave model thatassumes a fixed or minimum aqueous layer thickness (e.g., ≧2 μm), a3-wave theoretical tear film interference model is developed thatprovides variances in both LLT and ALT in the mathematical model of thetear film. Again, the lipid layer in the tear film model could bemodeled mathematically as a material having an index of refraction of1.48 or as fused silica substrate (SiO₂) having a 1.46 index ofrefraction. The aqueous layer could be modeled mathematically asMagnesium Flouride (MgF₂) having an index of refraction of 1.38. Abiological cornea could be modeled as fused silica with no dispersion,thereby resulting in a 3-wave model of air/SiO₂/MgF₂/SiO₂ (nodispersion). Once again, the most accurate results are obtained if themodel can include the refractive index and wavelength dispersion valuesof biological lipid material, biological aqueous material, and corneatissue, found from the literature, thus to provide a precise two-wavemodel of air/lipid/aqueous/cornea layers. Thus, a two-dimensional (2D)TFLT palette 430 (FIG. 29A) is produced for analysis of interferenceinteractions from specularly reflected light from the tear film. Onedimension of the TFLT palette 430 represents a range of RGB color valueseach representing a given theoretical LLT calculated by mathematicallymodeling the light source and the camera and calculating theinterference interactions from specularly reflected light from the tearfilm model for each variation in LLT 434 in the tear film interferencemodel. A second dimension of the TFLT palette 430 represents ALT alsocalculated by mathematically modeling the light source and the cameraand calculating the interference interactions from specularly reflectedlight from the tear film interference model for each variation in ALT432 at each LLT value 434 in the tear film interference model.

Post-Processing/TFLT Measurement

To measure TFLT, a spectral analysis of the resulting interferencesignal or image is performed during post-processing. In one embodiment,the spectral analysis is performed by performing a look-up in a tearfilm interference model to compare one or more interference interactionspresent in the resulting interference signal representing specularlyreflected light from the tear film to the RGB color values in the tearfilm interference model. In this regard, FIGS. 29A and 29B illustratetwo examples of palette models for use in post-processing of theresulting image having interference interactions from specularlyreflected light from the tear film using a 3-wave theoretical tear filminterference model developed using a 3-wave theoretical tear film model.In general, an RGB numerical value color scheme is employed in thisembodiment, wherein the RGB value of a given pixel from a resultingpre-processed tear film image of a patient is compared to RGB values inthe 3-wave tear film interference model representing color values forvarious LLTs and ALTs in a 3-wave modeled theoretical tear film. Theclosest matching RGB color is used to determine the LLT and/or ALT foreach pixel in the resulting signal or image. All pixels for a givenresulting frame containing the resulting interference signal areanalyzed in the same manner on a pixel-by-pixel basis. A histogram ofthe LLT and ALT occurrences is then developed for all pixels for allframes and the average LLT and ALT determined from the histogram (block348 in FIG. 28).

FIG. 29A illustrates an exemplary TFLT palette 430 in the form of colorsrepresenting the included RGB color values representing interference ofspecularly reflected light from a 3-wave theoretical tear film modelused to compared colors from the resulting image of the patient's tearfilm to estimate LLT and ALT. FIG. 29B illustrates an alternativeexample of a TFLT palette 430′ in the form of colors representing theincluded RGB color values representing interference of specularlyreflected light from a 3-wave theoretical tear film model used tocompare colors from the resulting image of the patient's tear film toestimate LLT and ALT. As illustrated in FIG. 29A, the TFLT palette 430contains a plurality of hue colors arranged in a series of rows for ALT432 and columns for LLT 434. In this example, there are 144 color hueentries in the palette 430, with nine (9) different ALTs and sixteen(16) different LLTs in the illustrated TFLT palette 430, althoughanother embodiment includes thirty (30) different LLTs. Providing anynumber of LLT and TFLT increments is theoretically possible. The columnsfor LLT 434 in the TFLT palette 430 contain a series of LLTs inascending order of thickness from left to right. The rows for ALT 432 inthe TFLT palette 430 contain a series of ALTs in ascending order ofthickness from top to bottom. The sixteen (16) LLT increments providedin the columns for LLT 434 in the TFLT palette 430 are 25, 50, 75, 80,90, 100, 113, 125, 138, 150, 163, 175, 180, 190, 200, and 225 nanometers(nm). The nine (9) ALT increments provided in the rows for ALT 432 inthe TFLT palette 430 are 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 3.0 and6.0 μm. As another example, as illustrated in FIG. 29B, the LLTs in thecolumns for LLT 434′ in the TFLT palette 430′ are provided in incrementsof 10 nm between 0 nm and 160 nm. The nine (9) ALT increments providedin the rows for ALT 432′ in the TFLT palette 430 are 0.3, 0.5, 0.08,1.0, 1.3, 1.5, 1.8, 2.0 and 5.0 μm.

As part of a per pixel LLT analysis 344 provided in the post-processingsystem 262 in FIG. 28, for each pixel in each of the pre-processedresulting images of the area or region of interest in the tear film, aclosest match determination is made between the RGB color of the pixelto the nearest RGB color in the TFLT palette 430 (block 345). The ALTsand LLTs for that pixel are determined by the corresponding ALTthickness in the y-axis of the TFLT palette 430, and the correspondingLLT thickness in the x-axis of the TFLT palette 430. As illustrated inFIG. 30, the TFLT palette 430 colors are actually represented by RGBvalues. The pixels in each of the pre-processed resulting images of thetear film are also converted and stored as RGB values, although anyother color representation can be used as desired, as long as thepalette and the image pixel data use the same representational colorspace. FIG. 30 illustrates the TFLT palette 430 in color pattern formwith normalization applied to each red-green-blue (RGB) color valueindividually. Normalizing a TFLT palette is optional. The TFLT palette430 in FIG. 30 is displayed using brightness control (i.e.,normalization, as previously described) and without the RGB valuesincluded, which may be more visually pleasing to a clinician if shown onthe display 174. The GUI utility 280 allows selection of differentpalettes by selecting a file in the palette file drop down 402, asillustrated in FIG. 19, each palette being specific to the choice of2-wave vs. 3-wave mode, the chosen source's spectrum, and the chosencamera's RGB spectral responses. To determine the closest pixel color inthe TFLT palette 430, a Euclidean distance color difference equation isemployed to calculate the distance in color between the RGB value of apixel from the pre-processed resulting image of the patient's tear filmand RGB values in the TFLT palette 430 as follows below, although thepresent disclosure is not so limited:Diff.=√((Rpixel−Rpalette)²⁺(Gpixel−Gpalette)²⁺(Bpixel−Bpalette)²)

Thus, the color difference is calculated for all palette entries in theTFLT palette 430. The corresponding LLT and ALT values are determinedfrom the color hue in the TFLT palette 430 having the least differencefrom each pixel in each frame of the pre-processed resulting images ofthe tear film. The results can be stored in RAM 258 or any otherconvenient storage medium. To prevent pixels without a close match to acolor in the TFLT palette 430 from being included in a processed resultof LLT and ALT, a setting can be made to discard pixels from the resultsif the distance between the color of a given pixel is not within theentered acceptable distance of a color value in the TFLT palette 430(block 346 in FIG. 28). The GUI utility 280 in FIG. 19 illustrates thissetting such as would be the case if made available to a technician orclinician. A distance range input box 408 is provided to allow themaximum distance value to be provided for a pixel in a tear film imageto be included in LLT and ALT results. Alternatively, all pixels can beincluded in the LLT and ALT results by selecting the ignore distanceselection box 410 in the GUI utility 280 of FIG. 19.

Each LLT and ALT determined for each pixel from a comparison in the TFLTpalette 430 via the closest matching color that is within a givendistance (if that post-processing setting 266 is set) or for all LLT andALT determined values is then used to build a TFLT histogram. The TFLThistogram is used to determine a weighted average of the LLT and ALTvalues for each pixel in the resulting image(s) of the patient's tearfilm to provide an overall estimate of the patient's LLT and ALT. FIG.31 illustrates an example of such a TFLT histogram 440. This TFLThistogram 440 may be displayed as a result of the shown LLT histogramselection box 400 being selected in the GUI utility 280 of FIG. 19. Asillustrated in FIG. 31, for each pixel within an acceptable distance,the TFLT histogram 440 is built in a stacked fashion with determined ALTvalues 444 stacked for each determined LLT value 442 (block 349 in FIG.28). Thus, the TFLT histogram 440 represents LLT and ALT values 442, and444, for each pixel. A horizontal line separates each stacked ALT value444 within each LLT bar.

One convenient way to determine the final LLT and ALT estimates is witha simple weighted average of the LLT and ALT values 442, 444 in the TFLThistogram 440. In the example of the TFLT histogram 440 in FIG. 31, theaverage LLT value 446 was determined to be 90.9 nm. The number ofsamples 448 (i.e., pixels) included in the TFLT histogram 440 was31,119. The frame number 450 indicates which frame of the resultingvideo image is being processed, since the TFLT histogram 440 representsa single frame result, or the first of a frame pair in the case ofbackground subtraction. The maximum distance 452 between the color ofany given pixel among the 31,119 pixels and a color in the TFLT palette430 was 19.9; 20 may have been the set limit (Maximum Acceptable PaletteDistance) for inclusion of any matches. The average distance 454 betweenthe color of each of the 31,119 pixels and its matching color in theTFLT palette 430 was 7.8. The maximum distance 452 and average distance454 values provide an indication of how well the color values of thepixels in the interference signal of the specularly reflected light fromthe patient's tear film match the color values in the TFLT palette 430.The smaller the distance, the closer the matches. The TFLT histogram 440can be displayed on the display 174 to allow a clinician to review thisinformation graphically as well as numerically. If either the maximumdistance 452 or average distance 454 values are too high, this may be anindication that the measured LLT and ALT values may be inaccurate, orthat the image normalization is not of the correct value. Furtherimaging of the patient's eye and tear film, or system recalibration canbe performed to attempt to improve the results. Also, a histogram 456 ofthe LLT distances 458 between the pixels and the colors in the TFLTpalette 430 can be displayed as illustrated in FIG. 32 to show thedistribution of the distance differences to further assist a clinicianin judgment of the results.

Other results can be displayed on the display 174 of the OSI device 170that may be used by a physician or technician to judge the LLT and/orALT measurement results. For example, FIG. 33 illustrates a thresholdwindow 424 illustrating a (inverse) threshold mask 426 that was usedduring pre-processing of the tear film images. In this example, thethreshold window 424 was generated as a result of the show thresholdwindow selection box 382 being selected in the GUI utility 280 of FIG.19. This may be used by a clinician to evaluate whether the thresholdmask looks abnormal. If so, this may have caused the LLT and ALTestimates to be inaccurate and may cause the clinician to discard theresults and image the patient's tear film again. The maximum distancebetween the color of any given pixel among the 31,119 pixels and a colorin the palette 430 was 19.9 in this example.

FIG. 34 illustrates another histogram that may be displayed on thedisplay 174 and may be useful to a clinician. As illustrated therein, athree-dimensional (3D) histogram plot 460 is illustrated. The cliniciancan choose whether the OSI device 170 displays this histogram plot 460by selecting the 3D plot selection box 416 in the GUI utility 280 ofFIG. 19, as an example, or the OSI device 170 may automatically displaythe histogram plot 460. The 3D histogram plot 460 is simply another wayto graphically display the fit of the processed pixels from thepre-processed images of the tear film to the TFLT palette 430. The planedefined by the LLT 462 and ALT 464 axes represents the TFLT palette 430.The axis labeled “Samples” 466 is the number of pixels that match aparticular color in the TFLT palette 430.

FIG. 35 illustrates a result image 428 of the specularly reflected lightfrom a patient's tear film. However, the actual pixel value for a givenarea on the tear film is replaced with the determined closest matchingcolor value representation in the TFLT palette 430 to a given pixel forthat pixel location in the resulting image of the patient's tear film(block 347 in FIG. 28). This setting can be selected, for example, inthe GUI utility 280 of FIG. 19. Therein, a “replace resulting image . .. ” selection box 412 is provided to allow a clinician to choose thisoption. Visually displaying interference interactions representing theclosest matching color value to the interference interactions in theinterference signal of the specularly reflected light from a patient'stear film in this manner may be helpful to determine how closely thetear film interference model matches the actual color value representingthe resulting image (or pixels in the image). Moreover, a selection box414 is provided to allow the clinician to select a showing of ahistogram of the images channels.

Ambiguities can arise when calculating the nearest distance between anRGB value of a pixel from a tear film image and RGB values in a TFLTpalette, such as TFLT palettes 430 and 430′ in FIGS. 29A and 29B asexamples. This is because when the theoretical LLT of the TFLT paletteis plotted in RGB space for a given ALT in three-dimensional (3D) space,the TFLT palette 469 is a locus that resembles a pretzel-like curve, asillustrated with a 2-D representation in the exemplary TFLT palettelocus 470 in FIG. 36. Ambiguities can arise when a tear film image RGBpixel value has close matches to the TFLT palette locus 470 atsignificantly different LLT levels. For example, as illustrated in theTFLT palette locus 470 in FIG. 36, there are three (3) areas of closeintersection 472, 474, 476 between RGB values in the TFLT palette locus470 even though these areas of close intersection 472, 474, 476represent substantially different LLTs on the TFLT palette locus 470.This is due to the cyclical phenomenon caused by increasing orders ofoptical wave interference, and in particular, first order versus secondorder interference for the LLT range in the tear films. Thus, if an RGBvalue of a tear film image pixel is sufficiently close to two differentLLT points in the TFLT palette locus 470, the closest RGB match may bedifficult to match. The closest RGB match may be to an incorrect LLT inthe TFLT palette locus 470 due to error in the camera and translation ofreceived light to RGB values. Thus, it may be desired to provide furtherprocessing when determining the closest RGB value in the TFLT palettelocus 470 to RGB values of tear film image pixel values when measuringTFLT.

In this regard, there are several possibilities that can be employed toavoid ambiguous RGB matches in a TFLT palette. For example, the maximumLLT values in a TFLT palette may be limited. For example, the TFLTpalette locus 470 in FIG. 36 includes LLTs between 10 nm and 300 nm. Ifthe TFLT palette locus 470 was limited in LLT range, such as 240 nm asillustrated in the TFLT palette locus 478 in FIG. 37, two areas of closeintersection 474, 476 in the TFLT palette 469 in FIG. 36 are avoided inthe TFLT palette 469 of FIG. 37. This restriction of the LLT ranges maybe acceptable based on clinical experience since most patients do notexhibit tear film colors above the 240 nm range and dry eye symptoms aremore problematic at thinner LLTs. In this scenario, the limited TFLTpalette 469 of FIG. 37 would be used as the TFLT palette in thepost-processing system 262 in FIG. 28, as an example.

Even by eliminating two areas of close intersection 474, 476 in the TFLTpalette 469, as illustrated in FIG. 37, the area of close intersection472 still remains in the TFLT palette locus 478. In this embodiment, thearea of close intersection 472 is for LLT values near 20 nm versus 180nm. In these regions, the maximum distance allowed for a valid RGB matchis restricted to a value of about half the distance of the TFLTpalette's 469 nearing ambiguity distance. In this regard, RGB values fortear film pixels with match distances exceeding the specified values canbe further excluded from the TFLT calculation to avoid tear film pixelshaving ambiguous corresponding LLT values for a given RGB value to avoiderror in TFLT measurement as a result.

In this regard, FIG. 38 illustrates the TFLT palette locus 478 in FIG.37, but with a circle of radius R swept along the path of the TFLTpalette locus 478 in a cylinder or pipe 480 of radius R. Radius R is theacceptable distance to palette (ADP), which can be configured in thecontrol system 240. When visualized as a swept volume inside thecylinder or pipe 480, RGB values of tear film image pixels that fallwithin those intersecting volumes may be considered ambiguous and thusnot used in calculating TFLT, including the average TFLT. The smallerthe ADP is set, the more poorly matching tear film image pixels that maybe excluded in TFLT measurement, but less pixels are available for usein calculation of TFLT. The larger the ADP is set, the less tear filmimage pixels that may be excluded in TFLT measurement, but it is morepossible that incorrect LLTs are included in the TFLT measurement. TheADP can be set to any value desired. Thus, the ADP acts effectively tofilter out RGB values for tear film images that are deemed a poor matchand those that may be ambiguous according to the ADP setting. Thisfiltering can be included in the post-processing system 262 in FIG. 28,as an example, and in step 346 therein, as an example.

Graphical User Interface (GUI)

In order to operate the OSI device 170, a user interface program may beprovided in the user interface system 278 (see FIG. 17A) that drivesvarious graphical user interface (GUI) screens on the display 174 of theOSI device 170 in addition to the GUI utility 280 of FIG. 19 to allowaccess to the OSI device 170. Some examples of control and accesses havebeen previously described above. Examples of these GUI screens from thisGUI are illustrated in FIGS. 39-45 and described below. The GUI screensallow access to the control system 240 in the OSI device 170 and tofeatures provided therein. As illustrated in FIG. 39, a login GUI screen520 is illustrated. The login GUI screen 520 may be provided in the formof a GUI window 521 that is initiated when a program is executed. Thelogin GUI screen 520 allows a clinician or other user to log into theOSI device 170. The OSI device 170 may have protected access such thatone must have an authorized user name and password to gain access. Thismay be provided to comply with medical records and privacy protectionlaws. As illustrated therein, a user can enter their user name in a username text box 522 and a corresponding password in the password text box524. A touch or virtual keyboard 526 may be provided to allowalphanumeric entry. To gain access to help or to log out, the user canselect the help and log out tabs 528, 530, which may remain resident andavailable on any of the GUI screens. After the user is ready to login,the user can select the submit button 532. The user name and passwordentered in the user name text box 522 and the password text box 524 areverified against permissible users in a user database stored in the diskmemory 268 in the OSI device 170 (see FIG. 17A).

If a user successfully logs into the OSI device 170, a patient GUIscreen 534 appears on the display 174 with the patient records tab 531selected, as illustrated in FIG. 40. The patient GUI screen 534 allows auser to either create a new patient or to access an existing patient. Anew patient or patient search information can be entered into any of thevarious patient text boxes 536 that correspond to patient fields in apatient database. Again, the information can be entered through thevirtual keyboard 526, facilitated with a mouse pointing device (notshown), a joystick, or with a touch screen covering on the display 174.These include a patient ID text box 538, patient last name text box 540,patient middle initial text box 542, a patient first name text box 544,and a date of birth text box 546. This data can be entered for a newpatient, or used to search a patient database on the disk memory 268(see FIG. 17A) to access an existing patient's records. The OSI device170 may contain disk memory 268 with enough storage capability to storeinformation and tear film images regarding a number of patients.Further, the OSI device 170 may be configured to store patientinformation outside of the OSI device 170 on a separate local memorystorage device or remotely. If the patient data added in the patienttext boxes 536 is for a new patient, the user can select the add newpatient button 552 to add the new patient to the patient database. Thepatients in the patient database can also be reviewed in a scroll box548. A scroll control 550 allows up and down scrolling of the patientdatabase records. The patient database records are shown as being sortedby last name, but may be sortable by any of the patient fields in thepatient database.

If a patient is selected in the scroll box 548, which may be an existingor just newly added patient, as illustrated in the GUI screen 560 inFIG. 41, the user is provided with an option to either capture new tearfilm images of the selected patient or to view past images, if past tearfilm images are stored for the selected patient on disk memory 268. Inthis regard, the selected patient is highlighted 562 in the patientscroll box 548, and a select patient action pop-up box 564 is displayed.The user can either select the capture new images button 566 or the viewpast images button 568. If the capture new images button 566 isselected, the capture images GUI 570 is displayed to the user under thecapture images tab 571 on the display 174, which is illustrated in FIG.42. As illustrated therein, a patient eye image viewing area 572 isprovided, which is providing images of the patient's eye and tear filmobtained by the video camera 198 in the OSI device 170. In this example,the image is of an overlay of the subtracted first and second tiledpattern images of the patient's tear film onto the raw image of thepatient's eye and tear film, as previously discussed. The focus of theimage can be adjusted via a focus control 574. The brightness level ofthe image in the viewing area 572 is controlled via a brightness control576. The user can control the position of the video camera 198 to alignthe camera lens with the tear film of interest whether the lens isaligned with the patient's left or right eye via an eye selectioncontrol 578. Each frame of the patient's eye captured by the videocamera 198 can be stepped via a stepping control 580. Optionally, or inaddition, a joystick may be provided in the OSI device 170 to allowcontrol of the video camera 198.

The stored images of the patient's eye and tear film can also beaccessed from a patient history database stored in disk memory 268. FIG.43 illustrates a patient history GUI screen 582 that shows a pop-upwindow 584 showing historical entries for a given patient. For each tearfilm imaging, a time and date stamp 585 is provided. The images of apatient's left and right eye can be shown in thumbnail views 586, 588for ease in selection by a user. The stored images can be scrolled upand down in the pop-up window 584 via a step scroll bar 590. Label namesin tag boxes 592 can also be associated with the images. Once a desiredimage is selected for display, the user can select the image to displaythe image in larger view in the capture images GUI 570 in FIG. 42.Further, two tear film images of a patient can be simultaneouslydisplayed from any current or prior examinations for a single patient,as illustrated in FIG. 44.

As illustrated in FIG. 44, a view images GUI screen 600 is shown,wherein a user has selected a view images tab 601 to display images of apatient's ocular tear film. In this view images GUI screen 600, bothimages of the patient's left eye 602 and right eye 604 are illustratedside by side. In this example, the images 602, 604 are overlays of thesubtracted first and second tiled pattern images of the patients tearfilm onto the raw image of the patient's eye and tear film, aspreviously discussed. Scroll buttons 606, 608 can be selected to move adesired image among the video of images of the patient's eye for displayin the view images GUI screen 600. Further, step and play controls 610,612 allow the user to control playing a stored video of the patient'stear film images and stepping through the patient's tear film images oneat a time, if desired. The user can also select an open patient historytab 614 to review information stored regarding the patient's history,which may aid in analysis and determining whether the patient's tearfilm has improved or degraded. A toggle button 615 can be selected bythe user to switch the images 602, 604 from the overlay view to just theimages 620, 622, of the resulting tiled interference interactions ofspecularly reflected light from the patient's tear films, as illustratedin FIG. 45. As illustrated in FIG. 45, only the resulting interferenceinteractions from the patient's tear film are illustrated. The user mayselect this option if it is desired to concentrate the visualexamination of the patient's tear film solely to the interferenceinteractions.

Many modifications and other embodiments of the disclosure set forthherein will come to mind to one skilled in the art to which thedisclosure pertains having the benefit of the teachings presented in theforegoing descriptions and the associated drawings. These modificationsinclude, but are not limited to, the type of light source orilluminator, the number of tiling groups and modes, the arrangement oftile groups, the type of imaging device, image device settings, therelationship between the illuminator and an imaging device, the controlsystem, the type of tear film interference model, and the type ofelectronics or software employed therein, the display, the data storageassociated with the OSI device for storing information, which may alsobe stored separately in a local or remotely located remote server ordatabase from the OSI device, any input or output devices, settings,including pre-processing and post-processing settings. Note thatsubtracting the second image from the first image as disclosed hereinincludes combining the first and second images, wherein like signalspresent in the first and second images are cancelled when combined.Further, the present disclosure is not limited to illumination of anyparticular area on the patient's tear film or use of any particularcolor value representation scheme.

Therefore, it is to be understood that the disclosure is not to belimited to the specific embodiments disclosed and that modifications andother embodiments are intended to be included within the scope of theappended claims. It is intended that the present disclosure cover themodifications and variations of this disclosure provided they comewithin the scope of the appended claims and their equivalents. Althoughspecific terms are employed herein, they are used in a generic anddescriptive sense only and not for purposes of limitation.

What is claimed is:
 1. An apparatus for imaging an eye, comprising: amulti-wavelength light source configured to emit light to an eye; and acontrol system configured to: (a) spatially modulate light from themulti-wavelength light source to project a first circular pattern ontothe eye, such that at least one first portion of the eye receivesemitted light from the multi-wavelength light source and at least onesecond portion of the eye does not receive the emitted light from themulti-wavelength light source; (b) receive at an imaging device, atleast one first image containing at least one first signal associatedwith an ocular property of the eye comprising the emitted lightreflected from the at least one first portion of the eye; (c) spatiallymodulate light from the multi-wavelength light source to project asecond circular pattern onto the eye, such that the at least one firstportion of the eye does not receive the emitted light from themulti-wavelength light source and the at least one second portion of theeye receives the emitted light from the multi-wavelength light source;(d) receive at the imaging device, at least one second image containingat least one second signal associated with the ocular property of theeye comprising the emitted light reflected from the at least one secondportion of the eye; and (e) subtract the at least one second image fromthe at least one first image to generate at least one resulting imagecontaining a resultant signal that represents the ocular property of theeye; wherein: the at least one first signal is optical wave interferenceof specularly reflected light from an ocular tear film combined with atleast one background signal; and the control system is configured toreceive the at least one first image by being configured to: capture afirst circular tiled pattern of the specularly reflected light includingthe at least one background signal from the at least one first portionof the ocular tear film in the at least one first image by the imagingdevice; and capture a second circular tiled pattern of the specularlyreflected light including the at least one background signal from the atleast one second portion of the ocular tear film in the at least onesecond image by the imaging device.
 2. The apparatus of claim 1, furthercomprising a light modulator system communicatively coupled to thecontrol system to spatially modulate light from the multi-wavelengthlight source to alternately project the first circular pattern and thesecond circular pattern onto the eye thereby generating the at least onefirst signal and the at least one second signal of the ocular property.3. The apparatus of claim 2, wherein the light modulator system includesa disk disposed between the imaging device and eye for sequentiallyprojecting the first circular pattern and the second circular patternonto the eye when the disk is illuminated, and wherein the disk includesa central aperture for the imaging device to receive light reflectedfrom the eye.
 4. The apparatus of claim 3, wherein the disk is patternedwith a plurality of concentric circles having alternating opaque andtranslucent sections with edges that form radials.
 5. The apparatus ofclaim 4, wherein the light modulator system further includes an electricmotor and a drive mechanism for rotating the disk to alternatelygenerate the first circular pattern while the imaging device capturesthe at least one first image containing the at least one first signal ofthe ocular property and to generate the second circular pattern whilethe imaging device captures the at least one second image containing theat least one second signal of the ocular property.
 6. The apparatus ofclaim 3, wherein the disk is a frusto-conical shaped disk having an openmajor base that faces the eye and an open minor base that faces theimaging device.
 7. The apparatus of claim 3, wherein the disk includespixels that when illuminated by the multi-wavelength light sourceproject the first circular pattern in response to a first control signaland project the second circular pattern in response to a second controlsignal.
 8. The apparatus of claim 1, wherein the multi-wavelength lightsource is comprised of a multi-wavelength Lambertian light sourceconfigured to uniformly or substantially uniformly illuminate the eye.9. The apparatus of claim 1, wherein the control system is furtherconfigured to display at least one of the at least one first image, theat least one second image, or the at least one resulting image on avisual display.
 10. The apparatus of claim 9, wherein the control systemis further configured to display the at least one resulting imageoverlaid onto the at least one of the at least one first image and theat least one second image on the visual display.
 11. The apparatus ofclaim 1, wherein the ocular property is comprised of a thickness of theocular tear film.
 12. The apparatus of claim 1, wherein the imagingdevice is configured to capture the at least one second image when themulti-wavelength light source is not illuminating the at least onesecond portion of the ocular tear film.
 13. The apparatus of claim 1,wherein the imaging device is configured to capture the at least onesecond image when the multi-wavelength light source is illuminating theat least one second portion of the ocular tear film.
 14. The apparatusof claim 1, wherein the control system is further configured to receivethe at least one second image containing the at least one backgroundsignal from the ocular tear film captured by the imaging device by beingconfigured to: capture the at least one background signal from the atleast one second portion in the first circular tiled pattern in the atleast one first image; and capture the at least one background signalfrom the at least one first portion of the second circular tiled patternin the at least one second image.
 15. The apparatus of claim 14, whereinthe control system is further configured to combine the at least onefirst image to the at least one second image to form the at least oneresulting image in a circular pattern containing the optical waveinterference of the specularly reflected light from the ocular tear filmwith the at least one background signal removed or reduced.
 16. Theapparatus of claim 1, wherein the control system is further configuredto: (f) convert at least a portion of the at least one resulting imagerepresenting the optical wave interference of the specularly reflectedlight from at least a portion of the ocular tear film into at least onecolor-based value; (g) compare the at least one color-based value to atear film layer optical wave interference model; and (h) measure a tearfilm layer thickness (TFLT) of the at least a portion of the ocular tearfilm based on the comparison of the at least one color-based value tothe tear film layer optical wave interference model.
 17. The apparatusof claim 16, wherein the control system configured to measure the TFLTof the at least a portion of the ocular tear film based on thecomparison of the at least one color-based value to the tear film layeroptical wave interference model further comprises measuring at least oneof a lipid layer thickness (LLT) and an aqueous layer thickness (ALT).18. The apparatus of claim 1, wherein the at least one first signal andthe at least one second signal are also associated with a second ocularproperty of the eye that is a corneal shape.
 19. The apparatus of claim18, wherein the first circular pattern and the second circular patternare generated by spatially modulating light with a disk comprised fromthe group consisting of a plurality of concentric circles havingalternating opaque and translucent sections including edges that formradials.
 20. The apparatus of claim 18, wherein the control system isfurther configured to subtract the at least one second image from the atleast one first image to generate the at least one resulting imagecomprising a Placido pattern that comprises a plurality of concentriccircles and radials.
 21. The apparatus of claim 1, wherein the ocularproperty is a corneal shape and the at least one first signal isassociated with corneal shape for the at least one first portion of theeye, and the at least one second signal is associated with the at leastone second portion of the eye.
 22. The apparatus of claim 21, whereinthe first circular pattern and the second circular pattern are generatedby spatially modulating light with a disk comprised from the groupconsisting of a plurality of concentric circles having alternatingopaque and translucent sections including edges that form radials. 23.The apparatus of claim 21, wherein the at least one first portion of theeye and the at least one second portion of the eye are comprised ofequal or approximately equal areas.
 24. The apparatus of claim 21,wherein the control system is further configured to subtract the atleast one second image from the at least one first image to generate theat least one resulting image comprising a Placido pattern that comprisesa plurality of concentric circles and radials.
 25. The apparatus ofclaim 24, wherein the control system is further configured to displaythe at least one resulting image of the Placido pattern on a visualdisplay.